bluuebunny/crossref_metadata_2025 huggingface dataset:
Difference in methylation patterns within the D15S9 region of chromosome 15qll–13 in first cousins with Angelman syndrome and Prader–Willi syndrome
Authors: Clayton‐Smith Jill , Driscoll Daniel J. , Waters Michael F. , Webb Tessa , Andrews Tony , Malcolm Sue , Pembrey Marcus E. , Nicholls Robert D.
Published: June 2005

Abnormalities of chromosome region 15qll–13 are associated with Angelman syndrome (AS) and Prader–Willi syndrome (PWS). Differences between the methylation patterns of the region of chromosome 15qll–13 which hybridizes to the highly conserved DNA, DN34, in normal individuals and in patients with AS and PWS have been described. We report on a family in which first cousins are affected by AS and PWS as a result of a familial paracentric inversion of 15qll–ql3. The results of the studies on this family demonstrate the differences in the methylation patterns in the 2 conditions and the phenomenon of genomic imprinting, whereby genetic information is expressed differently dependent on the parent of origin. © 1993 Wiley‐Liss, Inc.
Rieger syndrome revisited: Experimental approaches using pharmacologic and antisense strategies to abrogate EGF and TGF‐α functions resulting in dysmorphogenesis during embryonic mouse craniofacial morphogenesis
Authors: Slavkin Harold C.
Published: June 2005

The major manifestations of Rieger syndrome (RS), an autosomal dominant disorder, include absent maxillary incisor teeth, malformations of the anterior chamber of the eye, and umbilical anomalies [Aarskog et al., 1983: Am J Med Genet 15:29–38; Gorlin et al., 1990: “Syndromes of the Head and Neck” 3rd ed.]. Linkage of RS to human chromosome 4q markers has been identified with tight linkage to epidermal growth factor (EGF) [Murray et al., 1992: Nat Genet 2:46–48]. Mutations associated with genes of the EGF superfamily are implicated in malformations arising from abnormal development of the first branchial arch [Ardinger et al., 1989: Am J Hum Genet 45:348–353; Sassani et al., 1993: Am J Med Genet 45:565–569]. Down‐regulation of EGF during early mouse development results in ablation of tooth formation [Kronmiller et al., 1991: Dev Biol 147:485–488]. Since EGF, TGF‐α, and EGF receptor (EGFr) transcripts are expressed in the mouse first branchial arch and derivatives, experimental strategies were employed to investigate the consequences of down‐regulation of EGF translation and inhibition of EGF receptor during embryonic mandibular morphogenesis. Antisense inhibition of EGF expression produces mandibular dysmorphogenesis with decreased tooth bud size; these effects are reversed by the addition of exogenous EGF to the culture medium [Shum et al., 1993: Development 118:903–917]. TVrphostin RG 50864, which inhibits EGF receptor kinase activity, inhibits EGF or TGF‐α stimulation of tyrosine phosphorylation in a concentration‐dependent manner and severely retards mandibular development [Shum et al., 1993: Development 118:903–917]. These findings and the other evidence analyzed in this review support the hypothesis that RS represents abrogations of endogenous EGF signaling to regulate the size and shape of tooth formation during maxillary and mandibular morphogenesis. © 1993 Wiley‐Liss, Inc.
Anthropometric craniofacial pattern profiles in Down syndrome
Authors: Allanson J. E. , O'Hara P. , Farkas L. G. , Nair R. C.
Published: June 2005

A series of 21 anthropometric craniofacial measurements was performed on 199 individuals with Down syndrome (DS), age 6 months to 61 years. These were compared to age and sex‐matched normal standards, and Z score pattern profiles were constructed. These profiles confirmed brachycephaly and reduced ear length. With increasing age, maxillary growth was reduced in comparison to mandibular growth. Clinically, this was manifested by a change in facial shape from the characteristic round face of infancy to an oval shape in later life. Stepwise forward discriminant function analysis identified a subset of three variables (ear length, maxillary arc, and upper facial depth) which could accurately classify greater than 99% of the individuals in the combined sample of affected and unaffected individuals. Of the subjects with DS, 96.8% were classified correctly. These findings demonstrate the usefulness of anthropometric craniofacial pattern profiles in defining abnormal facial dimensions in particular syndromes and documenting the changes that occur with age. The technique should facilitate syndrome recognition, identification of carriers, and comparisons between syndromes. © 1993 Wiley‐Liss, Inc.
Lingual lesions and liabilities
Authors: Cohen M. Michael
Published: June 2005

Here, the uses and abuses of the tongue, lingual lesions and liabilities, and lingual calisthenics are reviewed. © 1993 Wiley‐Liss, Inc.
Cognitive skills in achondroplasia
Authors: Brinkmann G. , Schlitt H. , Zorowka P. , Spranger J.
Published: June 2005

Increased intracranial pressure and ventricular and subarachnoidal dilatation are common manifestations in achondroplasia. They rarely lead to major neurologic and/or psychomotor deficits and neurosurgical intervention is seldom needed. The present study was undertaken to detect signs of minor cerebral dysfunction and discuss possibilities of their prevention.

Thirty children with achondroplasia were compared to 3 control groups: their next‐born sibs, 30 children with other forms of dwarfism, and 30 children with normal height. Early development was assessed by means of questionnaires. Cognitive skills were evaluated with the German version of the Cognitive Abilities Test and the Lorge‐Thorndike Intelligence Test. Personality data were tested using standardized neuroticism, extraversion, and anxiety scales.

Children with achondroplasia had more frequent histories of delayed motor development, retarded speech development, and lower school grades in language‐related specialities. Psychometric testing disclosed total and subtest scores in the population‐based normal range. In comparison with their sibs and matched controls children with achondroplasia had significantly lower total scores mainly caused by low scores in the subtest “verbal comprehension”.

We conclude that verbal comprehension is significantly impaired in children with achondroplasia. This partial deficiency is probably related to frequent middle ear infections and resulting conductive hearing loss. Hypotonia with delayed oropharyngeal muscle coordination and parental response to an altered, more infantile instinctive releasing pattern may be contributing factors. © 1993 Wiley‐Liss, Inc.
Three cases of dup(10p)/del(10q) syndrome resulting from maternal pericentric inversion
Authors: Kulharya Anita S. , Schneider Nancy R. , Wilson Golder N.
Published: June 2005

Two families and 3 patients with dup(10p)/del(10q) syndrome segregating from a maternal pericentric inversion are described, including a stillborn female with Potter sequence and multicystic renal dysplasia. Comparison of 32 dup(10p) patients to 11 del(10)(q25) patients emphasized dolichocephaly, wide sutures, frontal bossing, micrognathia, and renal defects as distinguishing characteristics of the dup(10p) syndrome. The 3 new and 6 previously reported dup(10p)/del(10q) patients had several manifestations in common with the dup(10p) and del(10q) syndromes, but were more typical of dup(10p) syndromes, with respect to all 5 distinguishing characters. © 1993 Wiley‐Liss, Inc.
Rod‐cone dystrophy, sensorineural deafness, and renal dysfunction: An autosomal recessive syndrome?
Authors: Beighton Peter , Bartmann Lecia , Bingham Gavin , Sellars Sean
Published: June 2005

An autosomal recessive syndrome of progressive rod‐cone dystrophy, sensorineural deafness, and renal dysfunction was identified in 14 children in 9 Afrikaner families in South Africa. The renal involvement, which is of the Fanconi type, leads to rickets‐like skeletal changes and kidney failure. Each of the children was initially misdiagnosed as having retinitis pigmentosa or Usher syndrome, on a basis of minor retinal pigmentation. This condition, which appears to be a hitherto undocumented entity, warrants differentiation from these disorders. © 1993 Wiley‐Liss, Inc.
Pathologic characterization of short‐chain acyl‐CoA dehydrogenase deficiency in BALB/cByJ mice
Authors: Armstrong Dawna L. , Masiowski Michael L. , Wood Philip A.
Published: June 2005

BALB/cByJ mice have a deficiency of short‐chain acyl‐CoA dehydrogenase (SCAD) and are a useful model for studying the inborn errors of fatty acid metabolism which affect humans. Patients with some of these disorders present with hypoglycemia, hyperamonemia, and microvesicular fatty change of hepatocytes. In the present study we examined pathogen‐free, SCAD deficient BALB/cByJ mice and control BALB/cBy mice for biochemical and tissue changes following fasting or salicylate challenge. We observed mitochondrial swelling and microvesicular fatty changes in hepatocytes in mutant mice, especially severe following a fast. However, fasting did not alter their blood ammonia and there was no apparent clinical disease. Similarly, salicylates did not produce disease in the BALB/cByJ mice. We did detect in mice an alternative pathway for salicylate metabolism, by‐passing glycine conjugation which is the principal metabolic pathway in humans. © 1993 Wiley‐Liss, Inc.
On the variability of the Brachmann‐de Lange syndrome in seven patients
Authors: Leroy J. G. , Persijn J. , van De Weghe V. , van Heck R. , Oostra A. , De Bie S. , Craen M.
Published: June 2005

The results of the clinical and radiographic study of 7 patients support the view of a unimodal and rather narrow phenotypic spectrum in the Brachmann‐de Lange syndrome (BDLS) and reject the existence of a “classic” type of patient and a “mild phenotype” without upper limb defects who survive with moderate to severe mental retardation. Similarity among all patients is greater than their phenotypic differences. Strict clinical definition of the syndrome warrants easier access to the still unknown cause, most probably a single gene mutation with autosomal dominant inheritance. © 1993 Wiley‐Liss, Inc.
Hemimelia in Brachmann‐de Lange syndrome (BDLS): A patient with severe deficiency of the upper and lower limbs
Authors: Pfeiffer R. A. , Correll J.
Published: June 2005

We report on a male infant with Brachmann‐de Lange syndrome (BDLS) and ulnar hemimelia and monodactyly but also absence of both tibiae, the right distal femur being bifurcated. One similar observation was published earlier. The question is raised whether these malformations are coincidental or a rare component of BDLS. © 1993 Wiley‐Liss, Inc.
Congenital diaphragmatic hernia in the Brachmann‐de Lange syndrome
Authors: Cunniff Christopher , Curry Cynthia J. R. , Carey John C. , Graham John M. , Williams Charles A. , Stengel‐Rutkowski Sabine , Lüttgen Sabine , Meinecke Peter
Published: June 2005

We present 12 children with typical Brachmann‐de Lange syndrome and congenital diaphragmatic hernia. Affected children were more likely to be of low birth weight and to have major upper limb malformations. Hernia repair was attempted in 4 of these children, and only one survived past 12 months, Newborn infants with congenital diaphragmatic hernia should be examined carefully for evidence of the Brachmann‐de Lange syndrome because diagnosis of thes condition may influence their clinical management and prognosis. © 1993 Wiley‐Liss, Inc.
Gastrointestinal abnormalities: A significant cause of feeding difficulties and failure to thrive in Brachmann‐de Lange syndrome
Authors: Bull Marilyn J. , Fitzgerald Joseph F. , Hiefetz Stephen A. , Brei Timothy J.
Published: June 2005

Gastroesophageal abnormalities occur with increased frequency in patients with Brachmann‐de Lange syndrome (BDLS) and contribute to problems with feeding, emesis and failure to thrive. Comprehensive evaluation including longitudinal assessment of growth and development of 8 patients with BDLS was performed. Clinically significant feeding problems occurred in 6 of the 8 patients and the affected children were subsequently evaluated for gastrointestinal abnormalities. Findings in these patients included tracheal aspiration, esophageal dysmotility, gastroesophageal reflux, hiatal hernia, and esophagitis. Medical treatment was instituted where appropriate, and surgical treatment was performed if the problems did not resolve with medical treatment. Improvement in weight centiles occurred in all patients fed by nasogastric or feeding gastrostomy tube but only one patients appeared to experience increase in rate linear growth. Careful monitoring of symptoms and growth parameters, and prompt institution of appropriate medical and surgical measures can improve the health and physical outcome of many patients with BDLS. © 1993 Wiley‐Liss, Inc.
Syndrome of infantile osteopetrosis and Hirschsprung disease in seven children born to four consanguineous unions in two families
Authors: Dudin Anwar A. , Rambaud‐Cousson Annie
Published: June 2005

Two cases of Hirschsprung disease associated with infantile osteopetrosis are reported in 2 consanguineous families living in the same area. Both died early. © 1993 Wiley‐Liss, Inc.
Intrafamilial variability in Hurler syndrome and Sanfilippo syndrome type A: Implications for evaluation of new therapies
Authors: McDowell Geraldine A. , Cowan Tina M. , Blitzer Miriam G. , Greene Carol L.
Published: June 2005

Intrafamilial variability has not been reported previously in Hurler syndrome or Sanfilippo syndrome type A. We describe two families in which sibs with comparable deficiencies of α‐iduronidase (Hurler) or sulfamidase (Sanfilippo type A) activities in vitro nonetheless have divergence in clinical severity and disease progression. These cases underscore the need for caution in counseling as well as the limitations of using sibs as controls in evaluating the outcome of treatment. © 1993 Wiley‐Liss, Inc.
Isolation of a yeast artificial chromosome contig spanning the X chromosomal translocation breakpoint in a patient with Rett syndrome
Authors: Ellison Kimberly A. , Roth E. Jill , McCabe Edward R. B. , Chinault A. Craig , Zoghbi Huda Y.
Published: June 2005

Rett syndrome is a neurodevelopmental disorder observed exclusively in females. A de novo X;3 translocation was detected in a patient (TH) with Rett syndrome. The X chromosomal breakpoint maps to Xp21.3 between the distal end of the Duchenne muscular dystrophy (DMD) gene and the DXS28 (C7) locus. To determine if this translocation caused the Rett syndrome in this patient, our efforts focused on mapping and cloning of the X chromosomal breakpoint in this patient. Toward these goals, we generated a set of radiation‐reduced hybrid cell lines for the short arm of the X chromosome to use as a source for region‐specific markers. Using Alu‐PCR, 13 new DNA markers were isolated from a radiation‐reduced hybrid, which retained both DMD and DXS28. These markers were localized within Xp21 using DNA from males with various interstitial deletions in this region. Two new markers, K23‐2p and K23b‐1, were found to be closer flanking markers to the X chromosomal breakpoint than DMD and DXS28. Long range restriction mapping using K23‐2p and K23b‐1 determined that the maximum distance between them was 800 kb. Several of the new markers were developed into sequence tagged‐sites and were used to isolate yeast artificial chromosome (YAC) clones. A total of 22 YAC clones was isolated and characterized; these YACs were then developed into 3 large contigs in the Xp21.3 region. This effort resulted in the cloning of the region containing the X chromosomal translocation breakpoint of the Rett syndrome patient in a 170‐kb YAC clone. © 1993 Wiley‐Liss, Inc.
Dup(lq)(q42→qter) syndrome: Case report and review of literature
Authors: Kennerknecht Ingo , Barbi Gotthold , Rodens Klaus
Published: June 2005

We report on a patient with primordial growth retardation, mental retardation, and minor anomalies (triangular face, open sagittal suture, frontal bossing, telecanthus, upturned nose, micrognathia, and small mouth with downturned corners). The diagnosis of Russell‐Silver syndrome (RSS) had been considered but was abandoned when cytogenetic evaluation showed a partial trisomy lq or duplication lq (46,XY,15, + der(15)t(l;15)(q42;qter). Data from another 5 reports of dup(l)(q42→qter) do not allow delineation of a typical syndrome. However, individuals with dup(lq), del(15q), and Russell‐Silver syndrome share common manifestations (i.e., low birth weight, growth retardation, triangular face, low set/abnormal ears, micrognathia, renal anomalies). © 1993 Wiley‐Liss, Inc.
Familial occurrence of agonadism and multiple internal malformations in phenotypically normal girls with 46,XY and 46,XX karyotypes, respectively: A new autosomal recessive syndrome
Authors: Kennerknecht Ingo , Sorgo Wolfgang , Oberhoffer Renate , Teller Walter M. , Mattfeldt Torsten , Negri Giovanni , Vogel Walther
Published: June 2005

We report on 2 phenotypec sisters, one with 46,XY. the other with 46,XX. The 2 girls had similar related internal malformations, including agonadism, hypoplasia of the right pulmonary artery, hypoplasia of the right lung, isolated dextrocardia with complex vitium cordis, and diaphragmatic hernia (only sib 1) or omphalocele (only sib 2). This combination of malformations did not fit into any of the previously described syndromes. For this syndrome we suggest the acronym PAGOD ([hypoplasia of the] pulmo, and pulmonary artery, agonadism, omphalocele/diaphragmatic defect, dextrocardia). The occurrence of a basically similar set of malformations in 2 unlike sex is interpreted as evidence for autosomal recessive inheritance. The different gonosomal status excludes the Y chromosome as a responsible factor. The peculiar finding of a 46,XX sex chomosomr constitution combined with agonadism and an intact urogenital tract emphasizes the concept of secondary regression of Wolffian and Müllerian structures. The associated malformations of mesodermal structures can be interpreted as midline defects. We suggest that, from the developmental field perspective, secondary regression of midline structures including the gonadal anlage explains the pathogenesis reasonably well. © 1993 Wiley‐Liss, Inc.
Adams‐Oliver syndrome: A case with juvenile chronic myelogenous leukemia and chylothorax
Authors: Farrell S. A. , Warda L. J. , Laflair P. , Szymonowicz W.
Published: June 2005

We report on a patient with Adams‐Oliver syndrome and report new findings: a chylous pleural effusion and juvenile chronic myelogenous leukemia. Also, our patient had congenital heart disease, confirming that heart lesions are a manifestation in this syndrome. The major manifestations of this disorder are summarized. Included are cases not previously recognized as having Adams‐Oliver syndrome identified in a literature survey. Distal limb deficiency is commonest with more frequent and more severe involvement of the lower limbs. Scalp defects are the second commonest manifestation, while an underlying skull defect is not infrequent. Cutis marmorata telangiectatica and dilated scalp veins are significant signs of this condition. This review highlights unresolved questions about Adams‐Oliver syndrome. © 1993 Wiley‐Liss, Inc.
Stuttering as a phenotype for behavioral genetics research
Authors: Mellon Charles David , Umar Farah , Hanson Marvin L.
Published: June 2005

Stuttering is a broad behavioral phenotype with an adult prevalence of 0.7–1.0%. Family, twin, and segregation studies all indicate that stuttering has a large genetic component to its etiology. The relatively simple phenotype, the early onset, and the apparent rarity of phenocopies of adult stuttering all make stuttering a promising model for the study of the genetics of broad behavioral phenotypes. © 1993 Wiley‐Liss, Inc.
Mutational analysis of candidate genes in psychiatric disorders
Authors: Gejman Pablo V. , Gelernter Joel
Published: June 2005

A genetic hypothesis for a disease presupposes the existence of variation in the DNA sequences of affected individuals. A series of techniques known together as “mutational analysis” can be applied towards identifying new sequence variations in selected genes. These techniques can screen a large series of individuals for mutations efficiently, so it is not necessary to determine the nucleotide sequence in every DNA sample. DNA samples suspected of harboring sequence variants are then sequenced. Denaturing gradient gel electrophoresis techniques, single stranded conformation polymorphism paradigms, and chemical cleavage of mismatches are 3 procedures widely used for the molecular screening of mutations today. We discuss each of these techniques for mutation screening. © 1993 Wiley‐Liss, Inc.
Unipolar relatives in bipolar pedigrees: A search for indicators of underlying bipolarity
Authors: Blacker Deborah , Lavori Philip W. , Faraone Stephen V. , Tsuang Ming T.
Published: June 2005

In an effort to identify features indicative of underlying bipolarity within the unipolar relatives of bipolar probands, we compared unipolar relatives of bipolars with unipolar relatives of unipolars. Using data from the Collaborative Study of the Psychobiology of Depression, we compared a number of demographic and clinical features individually, and then developed a logistic regression model for the differences found. Unipolar relatives of bipolars were somewhat more likely to be male and to have subthreshold bipolar features, and less likely to have panic symptoms. In addition, they had a small but significant decrease in the number of depressive symptoms and a large decrease in all treatment indicators. A multiple logistic regression model for these differences was highly significant, but had limited ability to discriminate between the two groups. These differences are not large enough to effectively discriminate between the groups for the purposes of classification. These particular results may result from a number of factors, most likely the choice of comparison group. Nonetheless, the work demonstrates a potential method for the construction of caseness indices for use in genetic studies of bipolar and other psychiatric disorders. © 1993 Wiley‐Liss, Inc.
Alleles at the dopamine D4 receptor locus do not contribute to the genetic susceptibility to schizophrenia in a large Swedish kindred
Authors: Barr Cathy L. , Kennedy James L. , Lichter Jay B. , Van Tol Hubert H. M. , Wetterberg Lennart , Livak Ken J. , Kidd Kenneth K.
Published: June 2005

The discovery of a functional polymrphism within the dopamine D4 receptor gene (DRD4) has not only strengthened the hypotheses implicating DRD4 in the etiology of neuropyschiatic disorders, but also provided a genetic marker for testing these hypotheses. The possibility of the dopamine D4 receptor as a candidate gene for schizophrenia was investigated in a large Swedish kindred segregating for schizophrenia. Linkage to schizophrenia was tested by linkage analyses of 6 polymorphic markers (at 4 loci) in chromosome 11p15.5 including the dopamine D4 receptor (DRD4) and the tyrosine hydroxylase (TH) loci. Schizophrenia was excluded from close linkage to the DRD4 locus using two of the polymorphisms located within the dopamine D4 receptor gene. The first DRD4 polymorphism consists of variation in the number of a 48 bp imperfect direct repeat in the third exon; the second consists of a variable number of repeated G nucleotides in the first intron. In addition, some of the individuals homozygous for four or seven copies of 48 bp repeat alleles were tested for previously reported sequence variation among repeats. No single haplotype of the DRD4 alleles or haplotype of other markers in chromosome 11p15.5 was found to be common to the schizophrenic individuals in this family. Therefore, we find no evidence for linkage of the D4 receptor, or this region of 11p15.5, with genetic susceptibility to schizophrenia in this kindred. © 1993 Wiley‐Liss, Inc.
Summary of the third world congress on psychiatric genetics
Authors: Pato Carlos N. , Pato Michele T. , Kennedy James L.
Published: June 2005

A summary of the proceedings of the third world congress on psychiatric genetics is presented. The meeting was held in New Orleans on October 2–5, 1993 and brought together researchers from around the world. The International Society of Psychiatric Genetics sponsored and organized this meeting. Rapid advances of the last few years were reviwed and discussed in terms of their impact on the evolution of experimental design. The importace of definition of heritable clinical phenotypes, and the need to continue to enhance analytic methods were stressed as a prority for the field. © 1993 Wiley‐Liss, Inc.
Natural history of trisomy 18 and trisomy 13: II. Psychomotor development
Authors: Baty Bonnie J. , Jorde Lynn B. , Blackburn Brent L. , Carey John C.
Published: June 2005

Developmental data were abstracted from medical records on 50 trisomy 18 individuals ranging in age from 1 to 232 months and 12 trisomy 13 individuals ranging in age from 1 to 130 months. Data on the age when trisomy 18 and trisomy 13 children achieved developmental skills were collected from a larger group of 62 trisomy 18 individuals and 14 trisomy 13 individuals whose families filled out parent questionnaires. Developmental quotient (DQ), defined as developmental age divided by chronological age, averaged 0.18 for trisomy 18 and 0.25 for trisomy 13. There was a dramatic drop in DQ from infancy to later childhood. The highest DQs and the greatest variation in DQs were in the first 2–3 years of life. Developmental ages in 7 skill areas were significantly different, with daily living and receptive language having the highest values and motor and communication skills having the lowest. When chronological age was taken into account, there was no significant difference in DQs in the same 7 skill areas, although there was a trend that was similar to the pattern of differences with developmental age. Older children could use a walker, understand words and phrases, use a few words and/or signs, crawl, follow simple commands, recognize and interact with others, and play independently. Walking and some toileting skills were also reported for trisomy 13. Although individuals with trisomy 18 and trisomy 13 were clearly functioning in the severe to profound developmentally handicapped range, they did achieve some psychomotor maturation and always continued to learn. © 1994 Wiley‐Liss, Inc.
An infant with double trisomy (48,XXX, + 18)
Authors: Jaruratanasirikul Somchit , Jinorose Uraiwan
Published: June 2005

We report on an infant with double trisomy 48,XXX, + 18. She presented with manifestations of trisomy 18: prominent occiput, microphthalmia, small mouth, micrognathia, malformed ears, congenital heart defect, overlapping fingers, talipes equinovarus, and rockerbottom feet. An extra palmar crease was present only on the right hand. This patient was alive at 12 months. The clinical manifestations are compared with those of 10 previosly reported cases. © 1994 Wiley‐Liss, Inc.
Newly recognized autosomal recessive faciothoracoskeletal syndrome
Authors: Richieri‐Costa A. , Guion‐Almeida M. L. , Lauris J. R. P. , Ferreira D. M.
Published: June 2005

We report on 2 brothers, born to consanguineous parents presenting thin/long face, small ears, blepharophimosis, malar hypoplasia, long nec, pectus excavatum, brachy‐camptodactyly, and sacral dimple. We suspect that these patients represent a previously undescribed autosomal recessive syndrome. © 1994 Wiley‐Liss, Inc.
Spondyloepiphyseal dysplasia with nephrotic syndrome (Schimke immunoosseous dysplasia)
Authors: Šantavá Alena , Zapletalová Jiřina , Michálková Kamila , Hanáková Stanislava , Kopřiva František , Šantavý Jiří , Dušek Jaroslav , Kleinová Dušana
Published: June 2005

The first symptoms of immunoosseous dysplasia were growth retardation and myopia. Nephrotic syndrome was diagnosed at the age of 8 years. Skeletal roentgenograms showed spondyloepiphyseal dysplasia. In the renal biopsy there was nodular accumulations of PAS‐positive hyaline material at the base of the granular stalks. There was lymphopenia with decreased CD4 and CD8 subpopulations. The condition of the patient gradually worsened until she died unexpectedly at 10 years with clincal symptoms of encephalitis. Autopsy documented cytomegaloviral pneumonia and advanced mesangioproliferative glomerulonephritis. In the spleen there was PAS‐positive hyaline material massively infiltrating the walls of the central arterioles of the splenic follicles. There was marked depletion of lymphocytes in the spleen and in lymphnodes. The differential diagnosis of immunoosseous dysplasia in the framework of spondyloepiphyseal dysplasia is discussed. © 1994 Wiley‐Liss, Inc.
Preaxial brachydactyly with abduction of thumbs and hallux varus: A distinct entity
Authors: Sharma Anita K. , Haldar Ashutosh , Phadke Shubha R. , Agarwal S. S.
Published: June 2005

We describe a father and his daughter who had a unique pattern of preaxial brachydactyly, and unusual facial appearance. Both had short broad abducted thumbs and halluces. The second digits of both hands were also short and broad and those of feet were medially angulated. The radiographic findings were short first metacarpals and first metatarsals and hypoplastic phalanges of first two digits of hands and feet. A similar pattern of brachydactyly was described by Christian et al. [1972: Am J Hum Genet 24:694–701] and Mononen et al. [1992: Am J Med Genet 42:706–713]. Our patients differ from those described by Christian et al. in that they did not have any mental retardation and from those of Mononen et al. by the absence of short stature and epiphyseal and metaphyseal changes. The heterogeneity of this new type of brachydactyly remains to be resolved. © 1994 Wiley‐Liss, Inc.
Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma
Authors: McDonald M. , Maynard S. , Sheldon S. , Innis J.
Published: June 2005

This is the first reported case of an unbalanced chromosome rearrangement resulting in trisomy 5q35.5 → qter and monosomy 16p 13.3 → pter, in a boy with mental and growth retardation, minor anomalies, and a history of bilateral papillary thyroid carcinoma. This was the result of a familial balanced translocation. The clinical and cytogenetic manifestations of the case are presented and the possible role of the chromosomal rearrangement in the etiology of the thyroid carcinoma is discussed. © 1994 Wiley‐Liss, Inc.
Population screening for carrier status: Effects of test limitations on precision of carrier prevalence rates
Authors: Parker Robert A. , Phillips John A.
Published: June 2005

Because of genetic heterogeneity and ambiguity of test results, only rarely will carrier screening identify all carriers of a given autosomal recessive disorder. However, the fraction of carriers identified by the test can be estimated in a case frequency study. The population carrier rate then is the rate observed in a population screening study divided by the fraction of all defective alleles detected by the screening test, estimated in the case frequency study. For example, suppose 3% of a population are found to carry the AF508 mutation for cystic fibrosis (CF) during population screening. If a case frequency study in this same population finds that 75% of the alleles of CF cases represent the ΔF508 mutation, then the estimated population carrier rate is 4% (= .03/.75). The precision of this estimate involves the precision of both the fraction of carriers detected in the case frequency study and the proportion of carriers observed in the population screening study. Standard formulae for estimating the confidence interval and sample size consider only the variability in the population screening study. Since these formulae underestimate the true variability of the estimate of the population carrier rate, the sample size calculated for a population screening study is also underestimated. We present formulae which incorporate the variability in both factors, and illustrate the effect of this additional variability on confidence limits for estimtes and sample size when planning a study. © 1994 Wiley‐Liss, Inc.
McKusick‐Kaufman syndrome associated with esophageal atresia and distal tracheoesophageal fistula: A case report and review of the literature
Authors: Pul N. , Pul M. , Gedik Y.
Published: June 2005

A female infant with McKusick‐Kaufman syndrome associated with esophageal atresia and distal tracheoesophageal fistula is presented. To the best of our knowledge, this is the second report in the literature of this association. © 1994 Wiley‐Liss, Inc.
Adams oliver syndrome: A family with extreme variability in clinical expression
Authors: Bamforth J. S. , Kaurah P. , Byrne J. , Ferreira P.
Published: June 2005

We describe a mother and her 3 children with variable scalp defects and limb defects consistent with a diagnosis of Adams Oliver syndrome also presenting with additional anomalies including congenital heart disease, microcephaly, epilepsy, mental retardation, arrhinencephaly, hydrocephaly, anatomic bronchial anomalies, and renal anomalies. The clinical variation between the individuals is more pronounced than in previously reported families. © 1994 Wiley‐Liss, Inc.
Attitudes of physicians and genetics professionals toward cystic fibrosis carrier screening
Authors: Faden Ruth R. , Tambor Ellen S. , Chase Gary A. , Geller Gail , Hofman Karen J. , Holtzman Neil A.
Published: June 2005

With the identification of the cystic fibrosis (CF) gene and its major mutations in 1989, there has been considerable debate among health professionals as to whether population‐based carrier testing should be instituted. This paper presents the results of a survey to determine the attitudes of physicians and genetics professionals towards CF carrier testing. Factors associated with differences in attitudes also were examined.

A questionnaire was mailed to primary care physicians and psychiatrists in 10 states who graduated from medical school between 1950 and 1985. For comparison, medical geneticists and genetic counselors in the same states also received the questionnaire.

A total of 1,140 primary care physicians and psychiatrists (64.8%) and 280 medical geneticists and genetic counselors (79.1%) responded. Although 92% of respondents believed that a couple should be tested after asking about a test that detected 80% of carriers, only 43.9% of respondents believed such a test should be offered routinely. Those specialists most likely to have been involved in genetic services were most opposed to routine screening. The most important reason reported for opposition to routine screening was the consequences of an 80% detection rate. When presented with a hypothetical “error‐free” test, 75.9% of respondents favored routine testing.

Our findings suggest that there was little support for routinely offering the CF carrier test available at the time of this study among the physicians and professionals most involved in the provision of genetic services. © 1994 Wiley‐Liss, Inc.
RecTL: A complex allele of the glucocerebrosidase gene associated with a mild clinical course of Gaucher disease
Authors: Zimran Ari , Horowitz Mia
Published: June 2005

We describe 4 Jewish patients with type 1 Gaucher disease and the genotype N370S/recTL. They present either asymptomatic or mild Gaucher disease. RecTL is a complex allele that contains 4 single point mutations in the glucocerebrosidase gene: D409H, L444P, A456P, and V460V. Since patients who have the genotype N370S/L444P usually develop a moderate to severe course of Gaucher disease, and those who are homozygous for the D409H or the L444P mutations develop aggressive disease accompanied by neurological signs, it is of great importance to distinguish between the severe single base pair mutations and the mild complex recTL allele. This distinction should prove useful in assessing the natural history of Gaucher disease and in considering the indications for early enzyme replacement therapy. © 1994 Wiley‐Liss, Inc.
Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy
Authors: Mostacciuolo M. L. , Miorin M. , Vitiello L. , Rampazzo A. , Fanin M. , Angelini C. , Danieli G. A.
Published: June 2005

The occurrence of 2 different intragenic deletions (exons 10–44 and exon 45, respectively) is reported in 2 male relatives affected with Duchenne muscular dystrophy, both showing the same haplotype for DNA markers not included in the deleted segment.

The 2 different deletions seem to have occurred independently in the same X chromosome. This finding, together with other reports, suggests possibly an increased predisposition to mutations within the DMD locus in some families. Therefore, when dealing with prenatal diagnosis, the investigation on fetal DNA cannot be restricted only to the region in which a mutation was previously identified in the family. © 1994 Wiley‐Liss, Inc.
Informed consent and Huntington disease: A model for communication
Authors: Sharpe Neil F.
Published: June 2005

American and Canadian professional accreditation standards for medical genetics, and genetic counseling require certain abilities with regard to “communication.” What remains unclear is how such standards are to be interpreted in terms of appropriate clinical protocols, objectives, and values. These issues have significant medical and legal implications, particularly with regard to medical malpractice. From the perspective of genetic testing for Huntington disease, this paper identifies those clinical objectives and practices which may be described as constituting the appropriate standard of care for “communication,” and informed consent. © 1994 Wiley‐Liss, Inc.
Child with Sotos phenotype and a 5:15 translocation
Authors: Maroun Christiane , Schmerler Susan , Hutcheon R. Gordon
Published: June 2005

We report on a 4‐year‐old girl with Sotos phenotype and a de novo balanced translocation between the long arms of chromosome 5 and chromosome 15 [46,XX,t(5,15)(q35;q22)]. We suggest a relationship between genetic material at 5q35 or 15q22 and the expression of an autosomal dominant gene. © 1994 Wiley‐Liss, Inc.
New variant of chromosome 11
Authors: Aiello V. , Ricci N. , Palazzi P. , D'Agostino G. , Azzini G. , Calzolari E.
Published: June 2005

An additional C‐positive band in the centromeric region (p11) was observed in a man. By GTG‐ and RBA‐techniques it was positively stained but by QFQ‐technique the staining intensity was negative. Although he was identified through fetal loss in his wife, it apparently represents a familial variant whose clinical significance is unknown. © 1994 Wiley‐Liss, Inc.
Protelomeric sequences are deleted in cases of short arm inverted duplication of chromosome 8
Authors: Barber John C. K. , James Rowena S. , Patch Christine , Temple I. Karen
Published: June 2005

We present a patient with a de novo inverted duplication of the short arm of chromosome 8. Molecular analysis confirmed the cytogenetic suspicion of a simultaneous deletion of the tip of the short arm and indicated the maternal origin of the abnormality. This deletion made no detectable contribution to the phenotype of the patient which was comparable to that of previous cases of 8p duplication.

Similar investigations of inverted duplications involving other chromosomes may reveal unexpected deletions with significant phenotypic consequences. © 1994 Wiley‐Liss, Inc.
Further delineation of the Beemer–Langer syndrome using concordance rates in affected sibs
Authors: Lurie Iosif W.
Published: June 2005

Six familial cases of the Beemer–Langer syndrome (BLS) were analyzed to further elucidate the spectrum and frequency of anomalies observed in this disorder. Preaxial polydactyly was found in 3/6 affected sibs, and, therefore, its frequency previously may have been underestimated. Some patients, described as infants affected with the Majewski syndrome (MS) or “atypical” short rib‐poly‐dactyly conditions, may indeed have BLS. A high frequency of brain defects (16/26) and cleft tongue, oral frenula, and/or natal teeth (13/29) widens the list of typical findings in this syndrome. The specific type of tibial defect seems to be the most important discrimination of the MS and the BLS. © 1994 Wiley‐Liss, Inc.
Congenital heart defects in Aarskog syndrome
Authors: Fernandez Isabel , Tsukahara Masato , Mito Hiroshi , Yoshii Hideki , Uchida Masashi , Matsuo Kiyosato , Kajii Tadashi
Published: June 2005

We report on 10 Japanese individuals from 3 families affected with Aarskog syndrome. Pulmonary stenosis and ventricular septal defect with spontaneous closure were detected respectively, in 2 of them as an uncommon finding. A review documented 169 non‐Japanese cases (2 with congenital heart defects), while of 30 Japanese individuals reported till now, 4 (including ours) had cardiac anomalies. We propose that this combination is not coincidental and that in all cases of Aarskog syndrome a cardiac evaluation is indicated. © 1994 Wiley‐Liss, Inc.
RSH/SLO (“Smith‐Lemli‐Opitz”) syndrome: Historical, genetic, and developmental considerations
Authors: Opitz John M.
Published: June 2005

Thirty years after the publication of Smith et al. [1964: J Pediatr 64:210–217] of 3(4) cases of the RSH/SLO (“Smith‐Lemli‐Opitz”) syndrome and after the publication by Roux [1964: Arch Franç Pédiatr 21:451–464] on the teratogenic action of Triparanol, a defect of cholesterol metabolism was discovered by Tint and his co‐workers in the blood of the patients of Irons and Elias [Irons et al., 1993: Lancet 341:1414]. In this manner, the RSH syndrome has been identified as another metabolic multiple congenital anomalies/mental retardation (MCA/MR) syndrome (prototype Zellweger syndrome) in which deficient cholesterol synthesis must be held responsible for all parts of the syndrome, including blastogenetic and organogenetic malformations, minor anomalies, more or less severe abnormalities of CNS and PNS structure and function, postnatal failure to thrive, and, in some cases, stillbirth or infancy/childhood death. © 1994 Wiley‐Liss, Inc.
Nutritional requirements of infants and children with respect to cholesterol and related compounds
Authors: Barness Lewis A.
Published: June 2005

Cholesterol is an enigmatic, essential metabolite. Breast milk contains significant quantities of cholesterol, yet human infants thrive on cholesterol‐free diets. Recommendations to lower serum cholesterol are widespread, yet low serum cholesterol is associated with poorly understood morbidity. Serum cholesterol is increased with diets high in fat, yet dietary cholesterol has relatively little effect on serum concentrations. Smith‐Lemli‐Opitz syndrome, marked with extremely low serum cholesterol, may serve as a human model for the evaluation of absorption and metabolism of dietary cholesterol. © 1994 Wiley‐Liss, Inc.
Female pseudohermaphroditism with multiple caudal anomalies: Absence of Y‐specific DNA sequences as pathogenetic factors
Authors: Seaver Laurie H. , Grimes Judy , Erickson Robert P.
Published: June 2005

46,XX female pseudohermaphrodites have been previously described with nearly complete masculinization of the external genitalia and no apparent source of testosterone. Multiple malformations of internal genital, urinary, and gastrointestinal tracts are associated. We have evaluated four such infants with female pseudohermaphroditism and multiple caudal anomalies. Three cases had apparently normal chromosomes (46,XX); one had a 46,XX,del(10)(q25.3→qter) chromosome constitution. The chromosome breakpoint is in the region of PAX2, a developmentally important paired box gene which is expressed in urogenital tissue. Using the polymerase chain reaction, we screened for the presence of multiple Y specific sequences, including SRY (sex determining region, Y chromosome), that could explain masculinization of the external genitalia. All were negative for Y centromeric sequences, ZFY(Zinc finger Y), and SRY. Furthermore, there was no evidence for adrenal or other sources of testosterone. We suggest that the masculinization in these cases is the result of abnormal expression of genes which would normally be regulated by testosterone. © 1994 Wiley‐Liss, Inc.
Investigation of the potential role of genetic imprinting in Gilles de la Tourette syndrome
Authors: Furtado Sarah , Suchowersky Oksana
Published: June 2005

Genetic imprinting refers to the phenomenon whereby the precise expression of a specific trait (or disease) may depend on the sex of the transmitting parent. The purpose of the present project was to investigate the possibility for the involvement of genetic imprinting in Tourette syndrome (TS), a disease of the central nervous system in which many cases show evidence of an autosomal dominant mode of inheritance. The justification for the study arose from the noted variable expression of the associated symptoms in TS.

Through the method of chart review, information regarding sex of the transmitting parent, age of onset of motor tics, as well as associated symptoms, was gathered from patients with a clear family history of TS consistent with autosomal dominant mode of transmission. No evidence was found for genetic imprinting in TS. The potential criticisms and implications of this finding are discussed. © 1994 Wiley‐Liss, Inc.
Genetic linkage analysis of familial amyotrophic lateral sclerosis using human chromosome 21 microsatellite DNA markers
Authors: Rosen D. R. , Sapp P. , O'Regan J. , McKenna‐Yasek D. , Schlumpf K. S. , Haines J. L. , Gusella J. F. , Horvitz H. R. , Brown R. H.
Published: June 2005

Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord. We previously reported linkage of a gene for familial ALS (FALS) to human chromosome 21 using 4 restriction fragment length polymorphism DNA markers [Siddique et al.: N Engl J Med 324:1381–1384, 1991] and identified disease‐associated mutations in the superoxide dismutase (SOD)‐1 gene in some ALS families [Rosen et al.: Nature 362:59–62, 1993]. We report here the genetic linkage data that led us to examine the SOD‐1 gene for mutations. We also report a new microsatellite DNA marker for D21S63, derived from the cosmid PW517 [VanKeuren et al.: Am J Hum Genet 38:793–804, 1986]. Ten microsatellite DNA markers, including the new marker D21S63, were used to reinvestigate linkage of FALS to chromosome 21. Genetic linkage analysis performed with 13 ALS families for these 10 DNA markers confirmed the presence of a FALS gene on chromosome 21. The highest total 2‐point LOD score for all families was 4.33, obtained at a distance of 10 cM from the marker D21S223. For 5 ALS families linked to chromosome 21, a peak 2‐point LOD score of 5.94 was obtained at the DNA marker D21S223. A multipoint score of 6.50 was obtained with the markers D21S213, D21S223, D21S167, and FALS for 5 chromosome 21‐linked ALS families. The haplotypes of these families for the 10 DNA markers revealed recombination events that further refined the location of the FALS gene to a segment of approximately 5 megabases (Mb) between D21S213 and D21S219. The only characterized gene within this segment was SOD‐1, the structural gene for Cu, Zn SOD. © 1994 Wiley‐Liss, Inc.
Tetra‐amelia, lung hypo‐/aplasia, cleft lip‐palate, and heart defect: A new syndrome?
Authors: Başaran S. , Yüksel A. , Ermiş H. , Kuseyri F. , Aǧan M. , Yüksel‐Apak M.
Published: June 2005

We report on a family with two sons affected with tetra‐amelia, cleft lip‐palate, bilateral agenesis of lungs, and heart defects. These two cases support the previous suggestions that this complex entity may indeed represent a new syndrome. However, the mode of inheritance is still not clarified. © 1994 Wiley‐Liss, Inc.
Hypothalamic hamartoma in oral‐facial‐digital syndrome type VI (Váradi syndrome)
Authors: Stephan Mark J. , Brooks Kenneth L. , Moore Dan C. , Coll Edward J. , Goho Curt
Published: June 2005

Oral‐facial‐digital syndrome (OFDS) type VI (Váradi syndrome) is an autosomal recessive trait of orofacial anomalies, cerebellar dysgenesis, and polysyndactyly. Developmental anomalies of the posterior fossa, including cerebellar hypoplasia and variants of the Dandy‐Walker complex, are the most common central nervous system malformations reported in patients with this syndrome. We report hypothalamic hamartoma, supernumerary maxillary incisor, and precocious puberty in a boy with OFDS type VI. We propose that hypothalamic hamartoma is an occasional manifestation of OFDS type VI. © 1994 Wiley‐Liss, Inc.