bluuebunny/crossref_metadata_2025 huggingface dataset:
Thoracolumbosacral laminectomy in achondroplasia: Long‐term results in 22 patients
Authors: Pyeritz Reed E. , Sack George H. , Udvarhelyi George B. , Opitz John M. , Reynolds James F.
Published: June 2005

Neurologic problems caused by vertebral stenosis in the thoracolumbosacral (TLS) region are common in achondroplasia. Surgical decompression by means of laminectomy is recommended often, but its long‐term results have not been assessed. We reviewed the clinical history of 22 achondroplastic patients who had at least one TLS laminectomy performed before 1981, Symptoms predated the first TLS laminectomy by a mean of 2.3 years (range0.1–17 years). Preoperatively, 91% of patients had motor function impairment, 86% had sensory dysfunction, 86% had neurogenic claudication, 77% had radicular pain, 59% had symptomatic bladder dysfunction, and 32% had fecal incontinence. Only upper motor neurons were affected in 45%, only lower motor neurons in 27%, and both in 27%. Follow‐up after the first TLS laminectomy averaged 8 years. Of the 20 patients who initially improved neurologically, 12 had functional improvement for more than 5 years. However, 11 of these 12 subsequently regressed and 10 had additional laminectomies. Long‐term neurologic and functional improvement was associated with both a short duration of symptoms preopcratively and absence of cervical stenosis. Because of hypertrophic scarring, 9 patients developed compression at the site of the initial TLS laminectomy and required re‐operation 6.4 years (range 1–11 years) later. We conclude that TLS laminectomy is an effective treatment for spinal stenosis if performed early in the course of the neurologic syndrome. However, some patients have, or later develop, compression adjacent to the myelographic site of stenosis, and some develop hypertrophic scarring at the site of initial decompression. We therefore suggest that the first TLS laminectomy extend (1) 3 levels cephalad to the myelographic block, (2) at least to S2, and (3) laterally at least to the facets.
Interspecific genetic complementation analysis with fibroblasts from humans and four species of animals with Chediak‐Higashi syndrome
Authors: Penner Jocelyn D. , Prieur David J. , Opitz John M. , Reynolds James F.
Published: June 2005

Although the autosomal recessive disease Chediak‐Higashi syndrome (CHS) has been described in humans, cats, mink, cattle, mice, killer whales, blue foxes, and silver foxes, and these conditions appear quite similar, no direct evidence of the homology of this disease in the various species has been presented. To determine if CHS in humans, cats, mink, cattle, and mice is due to a mutant gene at the homologous genetic locus in each species, or alternatively, if these are merely similar syndromes, genetic complementa‐tion analysis after interspecific somatic cell (fibroblast) hybridization was performed. “Paracrystal” formation was the criterion used for the determination of complementa‐tion. The initial studies in this report were designed to characterize paracrystal formation in control and CHS fibroblasts of these five species. Most of the control fibroblasts from each species (91–96.6%) formed paracrystals upon incubation with 25 μg/ml of the microtubule depolymerizing agent vinblastine sulfate. A significantly (P < 0.05) smaller percentage of the CHS fibroblasts formed paracrystals after the same incubation (except CHS mice, with 90.2% paracrystals). It was found that 52% of the human CHS fibroblasts, 60% of cat CHS fibroblasts, 47% of mink CHS fibroblasts, and 53.8% of cow CHS fibroblasts formed paracrystals. For genetic complementation analysis, human CHS fibroblasts were fused to cat, mink, cow, or mouse CHS fibroblasts with polyethylene glycol. Control fusions were human CHS fibroblasts fused with human, cat, mink, cow, and mouse normal fibroblasts. The results of complementation analysis after the fusion of human CHS with cow CHS and human CHS with mouse CHS fibroblasts were inconclusive. A lack of complementa‐tion of human CHS with cat CHS and human CHS with mink CHS fibroblasts indicates that the disease is homologous in these species.
Extracellular matrix, cell skeletons, and embryonic development
Authors: Hay Elizabeth D.
Published: June 2005

During embryonic development, the extracellular matrix (ECM) promotes the production of differentiated products by epithelial cells and the migration of mesenchymal cells, and probably also plays a role in epithelial‐mesenchymal transformation. Here we examine the role of the cell skeleton (actin, microtubules, intermediate filaments) in mediating matrix effects on mesenchymal cell morphology, migration, and formation. The interaction of both epithelial cells and mesenchymal cells with ECM seems to involve the actin cortex, which is best developed in the base of the epithelial cell, where it attaches to underlying matrix via membrane‐intercalated receptors. To interact with the matrix, the fibroblast has appropriate ECM receptors and an actin cortex around the whole cell. The actin cortex is absolutely required for assumption of bipolar shape, elongation, and movement through the matrix. Since the cortex seems to be anchored to the matrix, it is unlikely that it moves during cell migration. A new hypothesis states that the microtubule‐ and intermediate filament‐rich endoplasm, containing the nucleus, moves past the actin cortex‐receptor‐matrix complex into the newly synthesized front end of the mesenchymal cell to effect forward movement. When epithelial cells transform into mesenchyme in the embryo, or when they are induced to do this in vitro, they switch from the keratin intermediate filament profile to one rich in vimentin, and the effect of cell matrix interaction on cell shape is profoundly altered. Vimentin‐actin interactions with ECM may be a major factor in the ability of a cell to become mesenchyma In concluding, we speculate that epithelial‐mesenchymal transformation involves a whole set of tissue specific effector genes whose expression might be mediated by a master gene system.
Ehlers‐Danlos syndrome type IV: A subset of patients distinguished by low serum levels of the amino‐terminal propeptide of type III procollagen
Authors: Steinmann Beat , Superti‐Furga Andrea , Joller‐Jemelka Helen I. , Cetta Giuseppe , Byers Peter H.
Published: June 2005

Serum levels of procollagen type III aminopropeptide (P‐III‐NP), a peptide released during conversion of type III procollagen to collagen, were abnormally low in six of 10 patients with Ehlers‐Danlos syndrome (EDS) type IV (arterial‐ecchymotic type) and low‐normal in 4. The serum P‐III‐NP levels correlated with the amount of type III procollagen secreted by the patients' cultured fibroblasts. Serum P‐III‐NP determination is a simple test that identifies a major subgroup of patients with this lifethreatening, dominantly inherited connective tissue disorder and may be especially helpful in making the diagnosis in children.
Skin is a window on heritable disorders of connective tissue
Authors: Holbrook Karen A. , Byers Peter H.
Published: June 2005

A skin biopsy contains the macromolecules present in most connective tissues: collagens, elastin, glycoproteins, and proteoglycans. The specific combination and assembly of these matrix components and their interactions with other structures (e.g., epidermal appendages, nerve and vascular networks) and cells are responsible for the distinction among specific regions of the dermis. The matrix components are interactive and interdependent and modification of one of them, by extrinsic (environmental) and/or intrinsic (systemic, genetic, age‐related) factors, may have consequences on the tissue as a whole. The skin, therefore, provides a window through which it is possible to examine how mutations in one connective tissue macromolecule can change the interations among matrix components and affect tissue structure and organization. Light and electron microscopic studies of skin from patients with inherited connective tissue disorders (e.g., Ehlers‐Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, cutis laxa) have led us to the following generalizations about what components change, how individual collagen or elastic fibers are altered and how individual alterations affect overall dermal organization: 1) There is a limited change in the repertoire of collagen fibrils in the skin; 2) there appears to be a greater range of abnormal structure in dermal elastic fibers than in the collagen fibrils; 3) the morphology of the fibroblastic cells may provide clues to the defect in matrix components; 4) similar structural abnormalities result from different molecular defect; 5) a molecular defect in one connective tissue molecule has consequences for the structural properties of other connective tissue components; and 6) although structural alterations in connective tissue fibers are rarely specific for a given disease, there are characteristic patterns of structural change in the matrix that may be used to confirm a diagnosis. These generalizations show that mutations rarely affect only a single aspect of macromolecular function and because of the interactions of matrix components in this complex organ (skin) often disturb the organization of the entire dermis. Genotype‐phenotype relationships are important to understand if effective therapies are to be designed. The structure of skin should provide the next level of integration in our efforts to determine how mutations produce disease.
Congenital myopathy with oculo‐facial abnormalities (Marden‐Walker syndrome)
Authors: Linder Nehama , Mathot Israel , Livoff Alexander , Glass Joseph , Bornstein Ilan , Gross Eva , Yatsiv Shaul , Sommer Annemarie
Published: June 2005

Marden‐Walker syndrome present in the neonatal period is characterized by oculo‐facial abnormalities, congenital myopathy, and contractures. A newborn infant with a similar pattern of anomalies is reported, and further evidence for autosomal recessive inheritance as well as new neuropathological findings are included.
Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy
Authors: Rapaport Debora , Passos‐Bueno Maria Rita , Brandão Lydia , Love Donald , Vainzof Mariz , Zatz Mayana
Published: June 2005

A total of 162 Duchenne (DMD) patients and two girls with a DMD phenotype were anlysed for deletions in the central region of the dystrophin gene in order to determine if there was a correlation between mental retardation (MR) and the pattern of deletion. Approximately 43% of the patients studied had deletions with two dystrophin cDNAs, cf23a and cf56a, and among 148 patients who were mentally assessed, 50% were mentally retarded. The average IQ in the group of patients with DNA deletions did not differ significantly from those patients with no detectable deletions. However, six unrelated DMD boys with MR showed an identical pattern of deletion. Our observations in the group of patients who had detected DNA deletions suggest that exon 52 of the dystrophin gene may be functionally significant in the manifestation of MR:70% (19/27) of patients with a deletion of this exon were mentally retarded, whereas only 38% (15/39) of MR patients had deletions not involving exon 52. This difference was statistically significant.
Acardiac amorphous twin with prune belly sequence in the co‐twin
Authors: Buntinx Inge M. , Bourgeois Nadia , Buytaert Philippe M. , Dumon Jan E.
Published: June 2005

We describe a twin with acardia acephalus or “Twin Reversed Arterial Perfusion Sequence” and prune belly sequence in the cotwin. In a former quite similar case a prune belly appearance of the co‐twin of an acardiac fetus was found to be secondary to the ascites caused by cardiac failure. In the present case, we are dealing with the prune belly sequence as a separate condition, given the fact there were no signs of ascites or cardiac failure. We also found associated anomalies:agenesis of the left ureter and kidney, dysplastic right kidney and anal atresia. Urinary tract obstruction has never been described in the co‐twin of an acardiac amorphous fetus.
Perspective of biochemical research in the neuronal ceroid‐lipofuscinosis
Authors: Rider J. Alfred , Dawson Glyn , Siakotos Aristotle N.
Published: June 2005

The search for biochemical abnormalities in the neuronal ceroid‐lipofuscinoses (NCL) or Batten disease was initiated with the discovery of normal levels of gangliosides in juvenile amaurotic idiocy. The primary goal of most biochemical studies has been to discover the unique biochemical marker for carriers and at‐risk individuals. Ceroid, the singular pathomorphologic trait of NCL, was isolated and shown to differ from a similar but normal product of aged cells, lipofuscin. In spite of the availability of stored product, the chemical analysis of ceroid has not elucidated the unique biochemical defect in the NCL, as has been the case for other lysosomal storage disorders. The NCL were thought to be a result oflipid peroxidationbecause ceroid is also found in disorders of impaired vitamin E metabolism or results from a diet deficient in the antioxidant, vitamin E. In addition, tissue analysis indicated losses of polyunsaturated fatty acids in affecteds and carriers, as well as the presence of a secondary product of lipid peroxidation, 4‐hydroxynonenal, in affected and carrier NCL dogs. With the exception of a fluorescent compound isolated from retinal ceroid, studies aimed at discovering thedisease‐specific fluorophoresof ceroid have been largely inconclusive. The discovery of elevated dolichols in urine and brain tissue of NCL patients led to another hypothesis, that the basic biochemical defect in NCL involved themetabolism of dolicholsand retinoids. However, the more recent view is that dolichol metabolism is secondary to the unknown NCL lesion. A possible role ofdeficient proteases or protease inhibitorsin NCL was developed after studies showed that inhibition of lysosomal thiol proteases would induce formation of autofluorescent lipopigments in brains of young rats. This initial discovery led to several reports of cathepsin deficiencies which, however, have not been reproducible. The discovery of abnormal storage of normal mitochondrial ATP synthase subunit C protein in NCL has been reported, but the reasons for the storage of this very hydrophobic protein were not apparent. A recent report found a modified amino acid, trimethyllysine in juvenile NCL ceroid. This may provide a reasonable explanation for the storage of the subunit C protein; i.e., the NCL defect may involve abnormal methylation and demethylation of proteins. Finally, localization of genes for 2 types of NCL mapping to 2 different chromosomes is a major advance in resolving the defect in NCL. Localization of genes for other inherited diseases has served as a prelude to the ultimate isolation and characterization of the genetic defect. With further progress in the biochemistry and molecular biology of NCL, the responsible gene product(s) may soon be discovered and characterized.
Evidence for lipase abnormality: High levels of free and triacylglycerol forms of unsaturated fatty acids in neuronal ceroid‐lipofuscinosis tissue
Authors: Banerjee Probal , Dasgupta Amitava , Siakotos Aristotle N. , Dawson Glyn
Published: June 2005

Total lipid obtained from normal and different forms of neuronal ceroid‐lipofuscinoses (NCL) tissues was analyzed by high performance thin layer chromatography (HPTLC). We observed a large (>6‐fold) increase in a lipid band corresponding to triolein for NCL dog pancreas and spleen and juvenile human NCL brain and infantile NCL spleen. The accumulation was less pronounced for the brain samples but apart from increased dolicholmonophosphate levels, other lipids appeared normal. Normal dog, goat, or human spleen contained virtually no triacylglycerol, and of the pathological controls, β‐mannosidosis goat spleen showed no triacylglycerol band at all. A sample of human spleen from a patient with lymphoma‐associated splenomegaly displayed a strong triacylglycerol band, but gas chromatography‐mass spectrometry (GC/MS) of the bands showed an equal increase in both saturated and unsaturated fatty acid containing triacylglycerols in the splenomegaly sample, in keeping with the notion of non‐specific fat deposition in damaged tissue. In contrast, in all the NCL samples (spleen, pancreas, and brain) a prominent increase in the proportion of unsaturated fatty acids was observed in both free fatty acid and/or triacylglycerol bands following GC/MS. The NCL‐English setter dog pancreas showed a major presence of oleic acid (18:1) (twofold increase) as compared to normal, while dog and infantile human NCL spleen samples and juvenile Batten brain (human) displayed a robust increase in linoleic acid (18:2) and sometimes in oleic acid and arachidonic acid (20:4) (for infantile human NCL spleen). For the infantile human NCL spleen sample an increase in linoleic acid in both free fatty acid (3.2‐fold) and triacylglycerol (10‐fold) was observed. This suggests a new mechanism by which polyunsaturated fatty acids can be transported to various parts of an NCL‐affected mammalian body in packages such as triacylglycerol and/or serum albumin:free fatty acid complex. Such polyunsaturated fatty acids could eventually lead to the ceroid‐lipofuscin pigment characteristic of NCl tissues through peroxidation to aldehyde with subsequent Schiff base formation. This could possibly explain the deposition of ceroid‐lipofuscin in widely different and non‐proximal tissues such as the pancreas and the brain.
Mitochondrial ATP synthase subunit c storage in the ceroid‐lipofuscinoses (Batten disease)
Authors: Palmer David N. , Fearnley Ian M. , Walker John E. , Hall Nicholas A. , Lake Brian D. , Wolfe Leonhard S. , Haltia Matti , Martinus Ryan D. , Jolly Robert D.
Published: June 2005

The ceroid‐lipofuscinoses (Batten disease) are neurodegenerative inherited lysosomal storage diseases of children and animals. A common finding is the occurrence of fluorescent storage bodies (lipopigment) in cells. These have been isolated from tissues of affected sheep. Direct protein sequencing established that the major component is identical to the dicyclohexylcarbodiimide (DCCD) reactive proteolipid, subunit c, of mitochondrial ATP synthase and that this protein accounts for at least 50% of the storage body mass. No other mitochondrial components are stored.

Direct sequencing of storage bodies isolated from tissues of children with juvenile and late infantile ceroid‐lipofuscinosis established that they also contain large amounts of complete and normal subunit c. It is also stored in the disease in cattle and dogs but is not present in storage bodies from the human infantile form.

Subunit c is normally found as part of the mitochondrial ATP synthase complex and accounts for 2–4% of the inner mitochondrial membrane protein. Mitochondria from affected sheep contain normal amounts of this protein. The P1 and P2 genes that code for it are normal as are mRNA levels. Oxidative phosphorylation is also normal.

These findings suggest that ovine ceroid‐lipofuscinosis is caused by a specific failure in the degradation of subunit c after its normal inclusion into mitochondria, and its consequent abnormal accumulation in lysosomes. This implies a unique pathway for subunit c degradation. It is probable that the human late infantile and juvenile diseases and the disease in cattle and dogs involve lesions in the same pathway.
Altered protein patterns in brains of children with neuronal ceroid lipofuscinosis
Authors: Wisniewski K. E. , Gordon‐Majszak W. , Maslinski S. , Heaney‐Kieras J.
Published: June 2005

The neuronal ceroid lipofuscinoses (NCL) are a group of inherited neurodegenerative diseases characterized by massive intralysosomal accumulation of storage materials. We have studied the protein patterns in 5 NCL, 5 control, and one Alzheimer disease brains. When protein patterns in NCL and control brain gray matter homogenates were examined by SDS‐PAGE, NCL brains showed an absence or greatly reduced amounts of the Mr 160–180 kDa component and reduced amounts of the Mr 29–36 kDa component. Concomitantly, an increase in several components with Mrs of 45–50 kDa was noted. The 180 kDa polypeptide appears to be a glycoprotein because it was bound to the lectins concanavalin A and Ulex europaeus.

Recently, the abnormal processing of amyloid protein precursor (APP) and its potential role in NCL have been suggested. Possible defects in tissue proteases and protease inhibitors may be considered responsible for the presence of these amyloid beta protein precursor fragments.

To examine this possibility we are using polyclonal antibodies to the C terminal 672–695 (APP) and monoclonal antibodies to inter‐α‐trypsin inhibitor. Polypeptides with molecular weights of approximately 35–38 kDa were detected in the NCL brain, but not in controls in both cases. These findings suggest abnormal protein processing in NCL brain tissue, disturbances in protein and glycocon‐jugate metabolism, impaired lysosomal function (i.e., metabolic enzyme and/or proteases/ proteinase inhibitor abnormalities), and the involvement of improperly processed APP.
Further delineation of the Simpson‐Golabi‐Behmel (SGB) syndrome
Authors: Gurrieri Fiorella , Cappa Marco , Neri Giovanni
Published: June 2005

The Simpson‐Golabi‐Behmel syndrome is an X‐linked condition characterized by pre‐ and postnatal overgrowth, “coarse” face, postaxial polydactyly, midline defects, and psycho‐motor development ranging from normal to mildly retarded. We report on an additional sporadic patient with novel manifestations, contributing to a more thorough delineation of this syndrome. © 1992 Wiley‐Liss, Inc.
Mucopolysaccharidosis type VII (β‐glucuronidase deficiency): A chronic variant with an oligosymptomatic severe skeletal dysplasia
Authors: de Kremer Raquel D. , Givogri Irene , Argaraña Carlos E. , Hliba Ernesto , Conci Rene , Boldini Catalina D. , Capra Ana P.
Published: June 2005

We report on a 20‐year‐old male with a β‐glucuronidase (GUSB) deficiency mucopoly‐saccharidosis. He had pectus carinatum, gross thoracic kyphoscoliosis, and hip dysplasia, a picture which became conspicuous after age 4 years. Hepatosplenomegaly, herniae, corneal clouding, and neurological abnormalities were absent. Although he had Alder‐type granulations in his polymorpho‐nuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. Electron microscopic examination of skin and gingival biopsies, leukocytes, and cultured skin fibroblasts showed numerous single membrane‐limited vacuoles either empty or filled with fibrillogranular material; this last tissue did not contain metachromatic granules. Radiographs demonstrated a distinct spondyloepiphyseal dysplasia in which the most striking changes were confined to the thoracic spine (flattening and collapse in T7, T8 and T10 vertebral bodies) and to the femoral capital epiphyses (irregularities and fragmentation). The activity of GUSB in the patient's serum, leukocytes, and fibroblasts was severely decreased; the GUSB activity in the serum and leukocytes from the parents and 2 asymptomatic sibs was subnormal. Immunoblot analysis showed very low levels of cross‐reactive material towards anti‐GUSB antiserum in the patient's leukocyte and fibroblast extracts. This patient was more severely affected in his skeleton than other described patients with an oligosymptomatic chronic form. This case broadens the clinical and biochemical picture associated with GUSB deficiency and may represent a new variant of the disease. © 1992 Wiley‐Liss, Inc.
Long‐term evaluation of a child with the branchio‐oculo‐facial syndrome
Authors: Schmerler Susan , Kushnick Theodore , Desposito Franklin
Published: June 2005

We report on the 12‐year development of a child with branchio‐oculo‐facial syndrome who was initially referred at age 5 months. Of note is his normal intelligence, regular class placement, hypernasal speech, and continued growth along the third centile. The importance of serial observations of patients with rare genetic disorders is emphasized. © 1992 Wiley‐Liss, Inc.
Portohepatic shunt in a down syndrome patient with an interchange trisomy 47,XY,−2,+der(2),+der(21)t(2;21)(p13;q22.1)mat
Authors: Kieran Mark W. , Vekemans Michel , Robb Laura J. , Sinsky Anna , Outerbridge Eugene W. , Der Kaloustian Vazken M.
Published: June 2005

A rare vascular portohepatic anomaly was identified in a Down syndrome patient with a 47,XY,−2,+der(2), + der(21)t(2;21)(p13;q22.1) mat chromosomal complement. This vascular defect involves a direct communication between the right portal vein and the inferior vena cava (IVC). We discuss the possibility that this vascular defect is a rare manifestation in Down syndrome. Alternatively, the existence of these 2 rare events in the same patient raises the possibility that they are causally related. © Wiley‐Liss, Inc.
Familial occurrence of renal and müllerian duct hypoplasia, craniofacial anomalies, severe growth and developmental delay
Authors: Davee Margaret A. , Moore Cynthia A. , Bull Marilyn J. , Hodes M. E.
Published: June 2005

Absence of the kidneys and of the Müllerian structures has been reported in many patients. We report on a brother and sister, born to nonconsanguineous parents, with renal hypoplasia, Müllerian duct hypoplasia, and strikingly similar facial abnormalities. Both sibs have severe growth and developmental retardation. We think that the unique clinical findings in these sibs represent a new syndrome. The embryological and genetic implications of this condition are discussed. © Wiley‐Liss, Inc.
Rambam–Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and bombay phenotype
Authors: Frydman Moshe , Etzioni Amos , Eidlitz‐Markus Tal , Avidor Israela , Varsano Itzhak , Shechter Yael , Orlin Jerome B. , Gershoni‐Baruch Ruth
Published: June 2005

We describe 2 Arab patients, both offspring of unrelated consanguineous matings, with unusual facial appearance, severe mental retardation, microcephaly, cortical atrophy, seizures, hypotonia, dwarfism, and recurrent infections with neutrophilia. Neutrophil motility was markedly decreased but the opsonophagocytic activity was normal. Both patients lack the red blood cell (RBC) H antigen and manifest the Bombay (hh) phenotype. Familial endocardial fibroelastosis and familial tetralogy of Fallot segregated independently in one family. The occurrence of the same syndrome in 2 unrelated families suggests that the various aspects of the disorder are the pleiotropic effects of a single mutation. Homozygosity‐by‐descent for a deletion involving contiguous genes may explain the findings in this syndrome. Alternatively, a mutation which involves an ubiquitous GDP fucose donor rather than the enzyme (α2‐L‐fucosyltransferase) or its substrate (glcNAc) may account for the pleiotropic manifestations in this syndrome. © Wiley‐Liss, Inc.
Innovative approach to genetic counseling services for the deaf population
Authors: Arnos Kathleen Shaver , Cunningham Margaret , Israel Jamie , Marazita Mary L.
Published: June 2005

Genetic service providers have stressed the importance of genetic counseling that is nondirective and specific to the personal needs of consultands. Successful genetic counseling for deaf persons often requires special provisions for complex family histories, syndromic conditions, and diversity in communication methods and cultural orientation.

The Gallaudet University Genetic Services Center (GSC) was established in 1984 to provide genetic education and counseling services to the deaf community. The GSC staff developed and implemented a standardized system of data collection (family and medical history), clinical evaluation by consultant clinical geneticists, and counseling in sign language. In addition to clinical services, an in‐depth educational program for professionals and consumers was developed and carried out. During a 6‐year period, over 220 educational presentations were made and 659 deaf persons were seen for genetic evaluation and counseling. Most of these persons were self‐referred. Sign language was the preferred means of communication of more than 90% of these individuals. A genetic cause of deafness was diagnosed in over 50% of the deaf consultands and was confirmed by segregation analysis, which had results similar to those reported for other studies of students in schools for the deaf.

Special materials and strategies were developed in order to provide genetic services that were sensitive to the cultural and linguistic differences of the deaf population. These included written and visual materials that contained culturally neutral terminology and training of all staff members in sign language and the culture of the deaf. © Wiley‐Liss, Inc.
Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia
Authors: Hecht Jacqueline T. , Blanton Susan H. , Wang Yaping , Daiger Steve P. , Horton William A. , Rhodes Craig , Yamada Yoshihiho , Francomano Clair A.
Published: June 2005

Patients with pseudoachondroplasia have a skeletal dysplasia with marked short stature. The most common cause of this condition is an autosomal dominant mutation, although autosomal recessive inheritance has been reported. Linkage to 2 cartilage‐specific candidate genes, type II collagen (COL2A1) and proteoglycan link protein genes (CRTL1), was tested in 9 autosomal dominant families with pseudoachondroplasia. Tight linkage to these candidate genes was excluded with LOD scores for COL2A1 of −2.45 at θ= 0.05 and for CRTL1 of −7.28 at θ= 0.001. Discordant inheritance of the disease phenotype with each of these genes was also observed. Thus, these 2 candidate genes can be excluded as the cause of disease in these families. © Wiley‐Liss, Inc.
Cardiovascular abnormalities in the oculo‐auriculo‐vertebral spectrum (Goldenhar syndrome)
Authors: Morrison J. , Mulholland H. C. , Craig B. G. , Nevin N. C.
Published: June 2005

We describe the phenotypic characteristics of 25 individuals with oculo‐auriculo‐vertebral spectrum (OAVS) and its variants, seen in Northern Ireland between 1969–1989, with special reference to cardiovascular defects. We report the type and prevalence of cardiovascular findings and also estimate the minimum prevalence rate of OAVS to be 1 in 45,000. © Wiley‐Liss, Inc.
Usefulness of a CACA repeat polymorphism in genotype assignments in Duchenne/Becker muscular dystrophy
Authors: Miller Marvin , Boehm Corinne , Cotton Matthew , Kazazian Haig H.
Published: June 2005

RFLP analysis in Duchenne/Becker muscular dystrophy (D/BMD) has been limited by the lack of informative marker loci at the 3′ end of the dystrophin gene. Recently a CACA repeat polymorphism was described in the 3′ untranslated end of the dystrophin gene which we have found helpful in genotype assignments of D/BMD families when an RFLP approach is required. The CACA repeat marker has 2 common alleles (1 and 2) that are easily visualized by a nonradioactive PCR method followed by polyacrylamide gel electrophoresis. We present 2 families which demonstrate the use of this polymorphism. Since 35–50% of females are heterozygous, this locus is a useful marker in RFLP analysis of D/BMD families. © Wiley‐Liss, Inc.
Confirmation of a cryptic unbalanced translocation using whole chromosome fluorescence in situ hybridization
Authors: Mewar Reema , Kline Antonie D. , Jackson Laird , Overhauser Joan
Published: June 2005

We report on a 7‐year‐old boy with minor anomalies, growth retardation, and developmental delay with an initial 46,XY,der(18)t(18;?)(q23;?) chromosome constitution. To determine the origin of the additional chromosome segment, several candidate regions were identified including 4q and 18q. Clinical comparison showed more similarities to individuals with partial dup(4q) than to those with a dup(18q). Whole chromosome fluorescence in situ hybridization (FISH) was used to demonstrate the correct origin of the translocated region, clarifying the karyotype as 46,XY,der(18)t(4;18) (q28.2;q22.2), thus generating information of clinical importance. This illustrates the use of whole chromosome FISH to identify chromosome regions that cannot be determined conclusively using standard cytogenetic banding techniques. © Wiley‐Liss, Inc.
Clinico‐pathological conference: A preterm infant with multiple congenital anomalies
Authors: Becerra Mario , Moya Fernando , Lacassie Yves , Stopa Aluizio , Craver Randall
Published: June 2005

A preterm female infant (28 weeks; 880 g) presented with bilateral ectrodactyly of the feet, small cleft palate, esophageal atresia and T‐E fistula, multivalvular dysplasia and VSD, thrombocytopenia, and other minor anomalies. Cytogenetic analysis showed trisomy 18. © Wiley‐Liss, Inc.
Craniofacial dysostosis, hypertrichosis, genital hypoplasia, ocular, dental, and digital defects: Confirmation of the Gorlin–Chaudhry–Moss syndrome
Authors: Ippel P. F. , Gorlin R. J. , Lenz W. , van Doorne J. M. , Bijlsma J. B.
Published: June 2005

We report clinical, orofacial and radiological manifestations in a 4‐year‐old girl and a 33‐year‐old female with the Gorlin–Chaudhry–Moss (GCM) syndrome. Typical findings in the GCM syndrome are short stature, stocky body build, midface hypoplasia, small eyes, downslanting palpebral fissures, conductive hearing loss, highly arched and narrow palate, malocclusion, abnormally shaped teeth, oligodontia, microdontia, low scalp hairline, hypertrichosis of scalp, face, trunk and limbs and genital hypoplasia. Radiological features include premature synostosis of the coronal suture, brachycephaly, and maxillary under‐development. Hypoplasia of the distal phalanges of fingers and toes (also present in the 2 original cases) represents a further manifestation of the GCM syndrome. © Wiley‐Liss, Inc.
Fragile X family with unusual digital and facial abnormalities, cleft lip and palate, and epilepsy
Authors: Loesch Danuta Z. , Hay David A. , Sheffield Leslie J.
Published: June 2005

We present a fragile X family with unusual clinical manifestations. These findings, which often occur in the X‐linked FG syndrome, include minor limb anomalies, cleft lip and palate, characteristic facial appearance, gastrointestinal problems and epilepsy, and intellectual disability.

In a total sample of 54 fra(X) families, the frequency of minor limb anomalies was estimated to be 32% in the affected males and 19% in the female heterozygotes. These anomalies tend to occur in several members of the same family, where some craniofacial abnormalities reported as characteristic of the FG syndrome have also been encountered. Possible mechanisms for the occurrence of these unusual manifestations in the fra(X) families are discussed. © 1992 Wiley‐Liss, Inc.
Fetal ultrasound abnormalities: Correlation with fetal karyotype, autopsy findings, and postnatal outcome—five‐year prospective study
Authors: Wilson R. D. , Chitayat D. , McGillivray B. C.
Published: June 2005

A 5‐year prospective prenatal study in 151 pregnancies with 152 malformed fetuses detected by ultrasound was evaluated cytogenetically. Thirty‐five fetuses (23%) had abnormal karyotypes. Specific anatomical fetal malformations identified by ultrasound increase the risk for fetal chromosome abnormalities. Risks of abnormal chromosomes in the fetus are present with both single and multiple anomalies including amniotic fluid volume although the risk is increased with specific anatomical systems and multiple malformations. An abnormal fetal karyotype was present in 17% with a single anatomical abnormality and 30% when two or more anatomical systems were involved. Fetal hydrops, duodenal atresia, and omphalocele were the most specific single ultrasound anomalies; fetal hydrops, IUGR, holoprosencephaly, congenital heart disease, diaphragmatic hernia, duodenal atresia, and omphalocele were the most specific multiple anomalies with abnormal amniotic fluid volume. Termination of pregnancy occurred in 32/58 patients diagnosed prior to the 20th week of pregnancy with most (31/32) having a chromosomal anomaly or severe fetal anomaly. Fetuses terminated after the 20th week had chromosomal (7/18) or lethal fetal anomalies (11/18). The most common aneuploidies were trisomy 21, trisomy 18, and 45,X. The decision to terminate the pregnancy was based in most cases on the fetal ultrasound findings. Correlation of ultrasound and clinical findings is important for accurate genetic counselling. © 1992 Wiley‐Liss, Inc.
Monozygotic twins concordant for late‐onset probable alzheimer disease with suspected alzheimer disease in four sibs
Authors: Karlinsky H. , Berg J. M. , Lennox A. , Ray P. N. , St. George‐Hyslop P. , Farrer L. A. , Percy M. E. , Andrews D. F. , Atack E. A.
Published: June 2005

Probable Alzheimer disease (AD) is described in 79‐year‐old male twins with monozygosity confirmed by DNA examination. The first twin to be affected began to show signs of intellectual deterioration at age 70. In the other, onset was at age 72. Four of their living sibs (current age range = 75–92) are also suspected to have AD. The possible roles of genetic and environmental factors in the development of AD in this sibship are discussed. © 1992 Wiley‐Liss, Inc.
Constriction bands and limb reduction defects in two newborns with fetal ultrasound evidence for vascular disruption
Authors: Van Allen Margot I. , Siegel‐Bartelt Jacqueline , Dixon Joanne , Zuker Ron M. , Clarke Howard M. , Toi Ants
Published: June 2005

Most structural anomalies attributed to vascular disruption have been inferred, though not proven, to be the result of disruptive events in utero. We report on 2 pregnancies with ultrasound evidence of disruptive events resulting in terminal limb “reduction” defects with constriction bands and other anomalies. In the first patient a fetal ultrasound study at 12 weeks post‐LMP demonstrated a monochorionic (MC) twin pregnancy with a nonviable co‐twin and no evidence of amniotic bands. At birth, there was a left cleft lip and palate, and terminal limb “reduction” defects with ring constrictions of the left hand and both feet. In the second patient, a routine fetal ultrasound study at 18 weeks post‐LMP identified a subhepatic cyst which subsequently resolved. Fetal ultrasound examination and neonatal computed tomography (CT) scan of the liver were consistent with a hepatic infarct due to emboli from the umbilical vein. At birth, patient 2 had acrosyndactyly of the left hand with ring constrictions of the digits and reduction of the left big toe. There was no evidence of abnormal amnion. Postnatal development has been normal in both cases.

We present ultrasound evidence supporting the hypothesis that vascular disruption from death of a co‐twin or from in utero embolic infarcts can cause: (1) terminal limb “reduction” defects and possibly cleft lip and palate; and (2) ring constrictions similar to those of “amniotic band disruption sequence” in the absence of an abnormal amnion. Serial pregnancy ultrasound studies are recommended for evaluation of the development of fetal structural anomalies following ultrasound evidence of a disruptive event in utero. © 1992 Wiley‐Liss, Inc.
Cytogenetic evidence for enhanced selective miscarriage of trisomy 21 pregnancies with advancing maternal age
Authors: Kratzer Paul G. , Golbus Mitchell S. , Schonberg Steven A. , Heilbron David C. , Taylor Robert N.
Published: June 2005

The effect of advancing maternal age on the risk of death of fetuses with certain chromosome abnormalities has been tested by comparing their frequency at the time of chorionic villus sampling (CVS) with that at amniocentesis. The frequency of chromosome abnormalities among women whose sole risk factor for a chromosome abnormality was advanced maternal age (≥35 years old) was determined in a pooled group of 15,147 CVS cases, of whom > 1/3 were from the initial 7,500 CVS cases at the University of California, San Francisco, and compared with a pooled group of 74,851 amniocentesis cases collected from the literature. The frequency of trisomy 21 not only increased with advancing maternal age as expected, but the slope of the increase was about 25% greater in the CVS group than in the amniocentesis group (P = 0.08 for the difference in slopes by a logistic statistical model and P = 0.04 by a normit model). Similar patterns were seen for trisomies 18 and 13, but the P values for the differences in slopes were much higher. These results suggest that the miscarriage rate of trisomy 21 during the gestational interval studied is selectively greater with advancing maternal age. The basis for the enhanced selective loss of trisomy 21 with maternal age may be a reduced ability of the ageing “maternal compartment” to compensate for abnormal conceptuses. © 1992 Wiley‐Liss, Inc.
Familial systematized epidermal nevus syndrome
Authors: Meschia James F. , Junkins Edward , Hofman Karen J.
Published: June 2005

Epidermal nevi are typically congenital but rarely familial. We report on a family in which 3 relatives have systematized epidermal nevi. The propositus also has evidence of a hemangioma and a hemangioendothelioma. Peripheral blood and skin fibroblast karyotypes of the propositus did not show evidence of mosaicism. Epidermal nevi have been associated with nondermatologic pathology, involving the nervous, vascular, and skeletal systems in sporadic cases. This report demonstrates that nondermatologic pathology can be also be associated with systematized epidermal nevi in a familial setting. The apparent skipping of generations may be explained by autosomal dominant inheritance with decreased penetrance. © 1992 Wiley‐Liss, Inc.
Double‐blind, placebo‐controlled crossover study of folinic acid (Leucovorin®) for the treatment of fragile X syndrome
Authors: Strom Charles M. , Brusca Rita M. , Pizzi William J.
Published: June 2005

We conducted a randomized, double‐blind, placebo‐controlled crossover study of folinic acid therapy (dl‐Leucovorin®, 15 mg/day) or placebo for males with Fragile X (fra(x)) syndrome. Twenty‐one patients were enrolled in the study. The treatment periods were 3 months in length. Patients were followed with chemistry panels and complete blood counts. No differences between placebo and treatment phases were noted in any laboratory parameter. Instruments to measure functioning were the Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test‐Revised, Conners Parent and Teaching Rating Scales, the ADD‐H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the investigators. At the crossover point, 2 parents requested to withdraw from the study because they felt their children had made dramatic gains during the first half of the study and had lost those gains after the crossover point. Both parents had accurately predicted that their sons were receiving folinic acid during the first half of the study. However, no statistically significant differences could be demonstrated between the treatment and placebo phases of the study with any instrument when the results were averaged over the entire cohort. After the conclusion of the study, approximately one‐half of the parents believed that their children had benefitted from the folinic acid therapy and elected to continue treatment. Thus far, no significant side effects have been noted from long‐term folinic acid therapy so we are offering all Fragile X patients a 3‐month trial of medication. © 1992 Wiley‐Liss, Inc.
Rapadilino syndrome
Authors: Vargas Fernando Regla , de Almeida José Carlos Cabral , Llerena Juan Clinton , Reis Dimas Fagundes
Published: June 2005

We report on a boy with severe radial hypoplasia, absent thumbs and patellae, short stature, persistent diarrhea, slender nose and normal intelligence as another example of the RAPADILINO syndrome. © 1992 Wiley‐Liss, Inc.
False‐negative prenatal diagnosis of restrictive dermopathy
Authors: Hamel B. C. J. , Happle R. , Steylen P. M. , Kollée L. A. A. , Stekhoven J. H. Schuurmans , Nijhuis J. G. , Rauskolb R. , Anton‐Lamprecht I.
Published: June 2005

Restrictive dermopathy is a rare autosomal recessive lethal skin dysplasia. It has been assumed that the characteristic morphologic abnormalities should allow a reliable prenatal diagnosis on fetal skin biopsies at about 20 weeks pregnancy. We report on a false‐negative prenatal diagnosis. © 1992 Wiley‐Liss, Inc.
Hyperphalangism, facial anomalies, hallux valgus, and bronchomalacia: A new syndrome?
Authors: Chitayat David , Haj‐Chahine Souad , Stalker Heather J. , Azouz E. Michael , Côté Aurore , Halal Fahed
Published: June 2005

We report on a boy with hyperphalangism, partial syndactyly, facial anomalies, and diffuse bronchomalacia, born to a nonconsan‐guineous French‐Canadian couple. To our knowledge, this is a hitherto undescribed syndrome. © 1993 Wiley‐Liss, Inc.
Reluctance to undergo predictive testing: The case of Huntington Disease
Authors: Quaid Kimberly A. , Morris Michael
Published: June 2005

The development of a presymptomatic test for Huntington Disease (HD) has enabled some persons at risk to determine whether or not they are gene carriers. The purpose of this study was to explore the reasons why those at risk choose not to be tested in a situation where testing is available and most of the test‐associated costs are covered by state funding. Subjects were also asked their levels of knowledge about testing, attitudes towards aspects of the testing protocols, and intentions towards testing once the gene for HD is found.

Sixty‐six individuals at risk for HD who had chosen not to be tested completed a mailed questionnaire. The most important reasons for not being tested were increased risk to children if one was found to be a gene carrier, absence of an effective cure, potential loss of health insurance, financial costs of testing, and the inability to “unndo” the knowledge.

Individuals comprising this sample were quite knowledgeable about predictive testing. Most supported the availability of testing despite the lack of a cure, the need for special counseling prior to testing, and the idea that testing should be a voluntary decision. Most said they would take the test if a treatment was available, if the mechanics of the test were simplified, or if the test was 100% accurate.

The risk to relatives, lack of treatment or cure, fear of losing one's health insurance, and the accuracy of the information to be gained from testing are important factors in the decision not to be tested. © 1993 Wiley‐Liss, Inc.
Preliminary definition of a “critical region” of chromosome 13 in q32: Report of 14 cases with 13q deletions and review of the literature
Authors: Brown Stephen , Gersen Steven , Anyane‐Yeboa Kwame , Warburton Dorothy
Published: June 2005

We report on 14 patients with partial deletions of chromosome 13q. These patients exhibit a wide spectrum of phenotypes. Deletions limited to proximal bands q13–q31 are associated with growth retardation but not with major malformations. We review the literature since 1975 and summarize 13q deletion cases which have a phenotype involving one or more major malformations and mental retardation. Analysis of the breakpoints of these cases, as well as those reported by us, supports the hypothesis that only deletions involving at least part of band q32 are associated with major malformations and digital abnormalities. Patients with more distal deletions have severe mental retardation but do not have major malformations or growth retardation. A group of patients in whom the breakpoint is stated to be within q32 has had an intermediate phenotype. This suggests that it may be possible to define subregions within q32 whose deletion is associated with particular developmental defects. © 1993 Wiley‐Liss, Inc.
Congenital defects of lower limbs and associated malformations: A population based study
Authors: Froster Ursula G. , Baird Patricia A.
Published: June 2005

As part of a detailed study of limb defects and associated patterns of congenital malformations, cases with lower limb deficiencies were analysed separately. We identified a total of 130 cases with deficiencies of the lower limbs without defects of the upper limbs. This gives an incidence of 1.07/10,000 livebirths, or 1/9,337 for this group of limb defects. Most common were femur deficiencies and deficiencies of the foot. A preponderance of males was found in the group of transverse defects of the leg (fibula/tibia deficiencies) and central axis deficiencies, while females had significantly more often longitudinal tibia defects and preaxial ray defects. © 1993 Wiley‐Liss, Inc.