bluuebunny/crossref_metadata_2025 huggingface dataset:
Batten disease and the ATP synthase subunit c turnover pathway: Raising antibodies to subunit c
Authors: Palmer D. N. , Bayliss S. L. , Westlake V. J.
Published: June 2005

Analysis of storage bodies in the ceroid‐lipofuscinoses (Batten disease) has demonstrated a high protein content suggestive of a proteinosis. Direct N‐terminal sequencing has shown that subunit c of mitochondrial ATP synthase is specifically stored in the disease in sheep and cattle, and in the human late infantile and juvenile diseases, as well as in 3 breeds of dogs. No differences have been found between the stored subunit c and that in normal mitochondria. No other mitochondrial components are stored. Different proteins, sphingolipid activator proteins (SAPs or saposins) A and D, are stored in the infantile disease.

Linkage studies have shown that different forms of ceroid‐lipofuscinosis are coded for on different genes on different chromosomes. The genes for subunit c, its production, its insertion into mitochondria, and mitochondrial function are normal. This suggests that underlying the various forms of the disease is a family of lesions in the normal pathway of subunit c turnover, after its normal insertion into the ATP synthase complex.

Antibodies to subunit c offer one way of mapping that pathway and detecting the sites of lesions. Specific antibodies have been raised against stored subunit c, using a liposomal adjuvant system which proved superior to classical adjuvants. These antibodies are also useful diagnostically, both in Western blotting and in immunocytochemistry.
Canine hereditary ceroid‐lipofuscinosis: Evidence for a defect in the carnitine biosynthetic pathway
Authors: Katz Martin L. , Siakotos Aristotle N.
Published: June 2005

The ceroid‐lipofuscinoses are a group of autosomal‐recessive hereditary lysosomal storage diseases that have been characterized in humans and other mammalian species. In a canine model for the juvenile form of the human disease, a major constituent of the storage bodies is the subunit c protein of mitochondrial ATP synthase that contains an ε‐N‐trimethyllysine (TML) residue. TML is a precursor in carnitine biosynthesis. To determine whether accumulation of the TML‐containing protein could result from a defect in the carnitine biosynthetic pathway, plasma carnitine and trimethyllysine levels were measured in homozygous affected, heterozygous carriers, and in normal dogs. When compared to normal animals, mean carnitine levels were reduced by 67% in affected and 50% in carrier dogs. Mean plasma TML levels were elevated almost 50% above control levels in the carriers, but were decreased by approximately 25% in the affected animals. The changes in plasma carnitine and TML levels in the carriers are consistent with the possibility that the disease involves a defect in the carnitine biosynthetic pathway. Secondary effects of the disease process may account for the apparently contradictory decrease in plasma TML levels in affected animals. © 1995 Wiley‐Liss, Inc.
Physical map of the region containing the gene for Batten disease (CLN3)
Authors: Järvelä Irma E. , Mitchison Hannah M. , Callen David F. , Lerner Terry J. , Doggett Norman A. , Taschner Peter E. M. , Gardiner R. Mark , Mole Sara E.
Published: June 2005

CLN3 has been mapped genetically to 16p12, to the interval between D16S288 and D16S383, a sex‐averaged genetic distance of 2.1 cM. Analysis of disease haplotypes for four microsatellite markers in this interval, D16S288, D16S299, D16S298, and SPN, has shown significant allelic association between one allele at each of these loci and CLN3. All four of the associated markers were used as nucleation sites in the isolation of genomic clones (YACs). A contig was assembled which contains 3 of the 4 associated markers and which confirmed the relative order of these markers. Marker D16S272 has been located on the physical map between D16S288 and D16S299. Restriction mapping has demonstrated the location of possible CpG islands. One gene, STP, has been localised on the YAC contig proximal to D16S298 and is therefore a candidate for CLN3. Other genes, including IL4R, SGLT2, and UQCRC2, have been excluded from this region. © 1995 Wiley‐Liss, Inc.
Analysis of Batten disease candidate genes STP and STM
Authors: Munroe Patricia B. , Mitchison Hannah M. , Dooley Thomas P. , Gardiner R. Mark , Mole Sara E.
Published: June 2005

We have sequenced a large proportion of the open reading frames (ORFs) of two phenol sulphotransferase gene transcripts (STP and STM) from three patients with Batten disease. This was done using reverse transcription and PCR amplification of total RNA followed by direct sequencing of the PCR products. No mutations or changes have been observed in either gene after sequencing 93% of the STP ORF and 72% of the STM ORF. Work is in progress to finish sequencing both genes which will allow the confirmation or exclusion of these phenol sulphotransferases having a role in the development of Batten disease. © 1995 Wiley‐Liss, Inc.
Phenol sulfotransferases: Candidate genes for Batten disease
Authors: Dooley Thomas P. , Probst Pam , Obermoeller R. Dawn , Siciliano Michael J. , Doggett Norman A. , Callen David F. , Mitchison Hannah M. , Mole Sara E.
Published: June 2005

Batten disease (juvenile‐onset neuronal ceroid lipofuscinosis; JNCL) is an autosomal recessive neurodegenerative disorder, characterized by the cytosomal accumulation of autofluorescent proteolipopigments in neurons and other cell types. The Batten disease gene (CLN3) has not yet been identified, but has been mapped to a small region of human chromosome area 16p12.1‐p11.2. We recently reported the fortuitous discovery that the cytosolic phenol sulfotransferase gene (STP) is located within this same interval of chromosome 16p. Since phenol sulfotransferase is expressed in neurons, can sulfate lipophilic phenolic compounds, and is mapped near CLN3, STP is considered as a candidate gene for Batten disease. YAC and cosmid cloning results have further substantiated the close proximity of STP and a highly related sulfotransferase (STM), encoding the catecholamine‐preferring enzyme, to the CLN3 region of chromosome 16p. In this report, we summarize some of the recent progress in the identification of two phenol sulfotransferase genes (STP and STM) as positional candidate genes for Batten disease. © 1995 Wiley‐Liss, Inc.
Carrier detection of Batten disease (Juvenile neuronal ceroid‐lipofuscinosis)
Authors: Taschner Peter E. M. , de Vos Nanneke , Post Jan G. , Meijers‐Heijboer E. Johanna , Hofman Irene , Loonen M. Christa B. , Pinckers Alfred J. L. G. , Bleeker‐Wagemakers Elisabeth M. , Gardiner R. Mark , Breuning Martijn H.
Published: June 2005

Batten disease, or the juvenile form of neuronal ceroid lipofuscinosis, is an autosomal recessive neurodegenerative disorder manifesting with progressive blindness, seizures, and dementia, leading to an early death. The CLN3 locus which is involved in Batten disease had been localized to chromosome 16p11.2. Linkage disequilibrium has been observed between CLN3 and polymorphic microsatellite markers D16S288, D16S299, and D16S298, making carrier detection and prenatal diagnosis by haplotype analysis possible. For the purpose of carrier detection, haplotypes from Dutch Batten patients and their families were constructed. Most patients share the same D16S298 allele, suggesting the presence of a founder effect in the Dutch population. In a large inbred Dutch family, in which Batten disease occurs with high frequency, haplotype analysis has been carried out with high accuracy for carrier detection. © 1995 Wiley‐Liss, Inc.
Bone marrow transplantation in Batten disease (Neuronal ceroid‐lipofuscinosis). Will it work? Preliminary studies on coculture experiments and on bone marrow transplant in late infantile Batten disease
Authors: Lake B. D. , Henderson D. C. , Oakhill A. , Vellodi A.
Published: June 2005

Lymphocytes from a patient with preclinical late infantile Batten disease were cultured alone and with lymphocytes from donors, and the fate of the curvilinear inclusions characteristic of the disease was monitored by electron microscopy. There was no evidence of transfer of deficient enzyme or factor that might have caused removal of the stored material, and the curvilinear profiles remained in the cultured cells without signs of degradation. Cells stimulated to divide with phytohaemaglutinin did not exhibit storage in culture suggesting that storage is a function of the age of the cell. The patient received a bone marrow transplant at 2 7/12 years while still clinically unaffected, and the effect on lymphocytes and cells in skin and rectal biopsies was monitored by electron microscopy over a period of 9 months until the donor marrow became displaced by the host cells. He has had one seizure and now has neurophysiological evidence of late infantile Batten's disease. Bone marrow transplant may have no effect on material already stored but might prevent further build‐up and halt the onset of the clinical symptoms although very recent studies on early (fetal) transplants in sheep with a form of Batten disease have shown no benefit. © 1995 Wiley‐Liss, Inc.
PCR‐based study of the presence of Y‐chromosome sequences in patients with Ullrich‐Turner syndrome
Authors: Coto Eliecer , Toral Joaquín F. , Menéndez María J. , Hernando Inés , Plasencia Ana , Benavides Ana , López‐Larrea Carlos
Published: June 2005

The presence of Y chromosome sequences in Ullrich‐Turner syndrome (UTS) patients has been suggested in previous work. Karyotype analysis estimated at about 60% of patients with a 45, X constitution and molecular analysis (Southern blot analysis with several Y chromosome probes and PCR of specific sequences) identified the presence of Y chromosome material in about 40% of 45, X patients.

We have developed a very sensitive, PCR‐based method to detect Y specific sequences in DNA from UTS patients. This protocol permits the detection of a single cell carrying a Y sequence among 105 Y‐negative cells. We studied 18 UTS patients with 4 Y‐specific sequences. In 11 patients we detected a positive amplification for at least one Y sequence. The existence of a simple and sensitive method for the detection of Y sequences has important implications for UTS patients, in view of the risk for some of the females carrying Y‐chromosome material of developing gonadoblastoma and viriliza‐tion. Additionally, some of the UTS associated phenotypes, such as renal anomalies, could be correlated with the presence of Y chromosome specific sequences. © 1995 Wiley‐Liss, Inc.
Supernumerary chromosome marker (1) in a developmentally delayed child
Authors: Lanphear Nancy , Lamb Allen , Oppenheimer Sonya , Soukup Shirley
Published: June 2005

A 15‐month‐old boy with mild developmental delay and several minor anomalies was found to be mosaic 46, XY/47, XY, +mar(l). The marker r(l) was a small de novo ring identified by FISH with a painting type DNA probe. © 1995 Wiley‐Liss, Inc.
Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature
Authors: Arn Pamela Hawks , Younie Linda , Russo Suzanne , Zackowski Joleen L. , Mankinen Carl , Estabrooks Laurel
Published: June 2005

We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocen‐tric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious. © 1995 Wiley‐Liss, Inc.
De novo apparently balanced reciprocal translocation between 5q1l.2 and 17q23 associated with Klippel‐Feil anomaly and type A1 brachydactyly
Authors: Fukushima Yoshimitsu , Ohashi Hirofumi , Wakui Keiko , Nishimoto Hiroshi , Sato Masato , Aihara Toshinori
Published: June 2005

We report on a girl with Klippel‐Feil anomaly, type Al brachydactyly, and minor facial anomalies. She has an apparently balanced de novo reciprocal translocation between 5q1l.2 and 17q23. The possible significance of this chromosomal abnormality is discussed. © 1995 Wiley‐Liss, Inc.
Dominant inheritance in two families with familial Mediterranean fever (FMF)
Authors: Yuval Y. , Hemo‐Zisser M. , Zemer D. , Sohar E. , Pras M.
Published: June 2005

Familial Mediterranean fever (FMF) is an autosomal‐recessive disease which affects almost exclusively people of Mediterranean and Middle Eastern origin. We examined the possibility of a dominant inheritance of FMF among our 3,000 patients in Israel.

Two hundred forty FMF patients were members of 77 families in which the disease affected more than one generation. In 75 of these families the occurrence of FMF in more than one generation was found to be consistent with a recessive mode of inheritance due to a high gene frequency (q) and consanguinity among parents of the patients.

In 2 families, one of Ashkenazi and the other of Georgian Iraqi origin, in which FMF occurred in 4 consecutive generations, the mode of inheritance could be explained only by autosomal‐dominant inheritance. © 1995 Wiley‐Liss, Inc.
Variable penetrance of hypogonadism in a sibship with Kallmann syndrome due to a deletion of the KAL gene
Authors: Parenti Giancarlo , Rizzolo Maria Grazia , Ghezzi Monica , Maio Salvatore Di , Sperandeo Maria Pia , Incerti Barbara , Franco Brunella , Ballabio Andrea , Andria Generoso
Published: June 2005

We report on the clinical and molecular characterization of 3 sibs with X‐linked ichthyosis and variable expression of Kallmann syndrome. One of the affected brothers had mild hyposmia and showed normal pubertal progression. However, we demonstrated the same partial deletion of the X‐linked Kallmann gene, sparing the first exon in the mildly affected patient as well as in one of his severely affected brothers. © 1995 Wiley‐Liss, Inc.
Two pedigrees of autosomal dominant atrioventricular canal defect (AVCD): Exclusion from the critical region on 8p
Authors: Amati Francesca , Mari Aldo , Mingarelli Rita , Gennarelli Massimo , Digilio Maria Cristina , Giannotti Aldo , Marino Bruno , Novelli Giuseppe , Dallapiccola Bruno
Published: June 2005

Atrioventricular canal defects (AVCD) constitute the predominant congenital heart defect in Down syndrome. For this reason, a candidate gene involved in atrioventricular canal development was previously searched and excluded in dominant pedigrees of AVCD, using linkage analysis of polymorphisms from chromosome 21. Because of the striking association between 8p deletion and AVCD, a search for an AVCD gene was carried out in two pedigrees of individuals with autosomal dominant AVCD using a set of DNA markers of the 8pter→ql2 region. These two families include affected individuals and subjects who have transmitted the defect but are not clinically affected. Two‐point lod scores were significantly negative for all markers at penetrance levels of 90% and 50%. Multipoint analysis excluded the region covered by the markers LPL‐D8S262 and 30 cM to either side of this area. This result corroborates heterogeneity of this heart defect and indicates that the genetic basis of familial AVCD is different from AVCD associated to either trisomy 21 or 8p deletion. © 1995 Wiley‐Liss, Inc.
XXY male with X‐linked dominant chondrodysplasia punctata (Happle syndrome)
Authors: Sutphen Rebecca , Amar Marcelo J. , Kousseff Boris G. , Toomey Kathleen E.
Published: June 2005

Happle syndrome is an X‐linked dominant disorder with presumed lethality in hemizy‐gous males; familial occurrence is rare. We describe a family with Happle syndrome affecting individuals in 3 generations. A man in this family is the first known male patient with Happle syndrome. He is severely affected; this may be due to his 47, XXY kary‐Otype. © 1995 Wiley‐Liss, Inc.
Short tandem repeat polymorphism linkage studies in a new family with X‐linked mental retardation (MRX20)
Authors: Lazzarini Alice , Stenroos Edward S. , Lehner Thomas , McKoy Vershon , Gold Bert , McCormack Michael K. , Reid Cheryl S. , Ott Jurg , Johnson William G.
Published: June 2005

A family with X‐linked recessive mental retardation (XLMR) without other obvious manifestations (MRX20) was studied with 14 short tandem repeat polymorphism (STRP) markers. Two‐point lod scores above 3 were obtained with DXS1003, DXYS1, DXS3, and DXS458. A multipoint lod score of 4.25 was obtained with peak at DXS1003. Recombination events identify a 55.6 cM interval between DXS1068 and DXS454, while a one unit support interval identifies 40 cM between MAOA and DXS458. © 1995 Wiley‐Liss, Inc.
Small patella syndrome
Authors: Kozlowski Kazimierz , Nelson John
Published: June 2005

We report on 2 sporadic cases of small patella syndrome (coxo‐podo‐patellaire syndrome) most probably representing new mutations. Both children showed retarded patellar bone age (small patellae in Patient 1 and absent patellae in Patient 2) and pelvic abnormalities. Patient 1 who was fully investigated had an unusual facies with characteristic morphological abnormalities of the forefoot and generalized bone changes. Patient 2 was not available for examination and only X‐ray films of his knees, pelvis, and chest were available. These were all abnormal. He was said to have an “unusual facies” with flattened nose and prominent forehead but no further information was available.

We think that small patella syndrome (coxo‐podo‐patellaire syndrome) is a generalized bone dysplasia with morphological and diagnostic radiographic appearances. © 1995 Wiley‐Liss, Inc.
De novo nonreciprocal translocation 1;8 confirmed by fluorescent in situ hybridization
Authors: Wiley John E. , Stout Janice C. , Palmer Shane M. , Kushnick Theodore
Published: June 2005

Constitutional nonreciprocal translocations are extremely rare, and even their existence is controversial. We report on a newborn infant with a de novo nonreciprocal translocation between chromosomes 1 and 8 resulting in 1q42.3 deletion syndrome. Fluorescent in situ hybridization with whole chromosome paints confirmed the conventional cytogenetic diagnosis. © 1995 Wiley‐Liss, Inc.
Association of kyphomelic dysplasia with severe combined immunodeficiency
Authors: Corder W. Thomas , Hummel Marybeth , Miller Christopher , Wilson Nevin W.
Published: June 2005

Kyphomelic dysplasia is a distinct, rare, skeletal dysplasia with short angulated femora, bowing of long bones, short ribs, narrow thorax, and metaphyseal abnormalities. While immune deficiency occurs in other short stature/short‐limb skeletal dysplasias and cartilage‐hair hypoplasia, it has not been described with kyphomelic dysplasia. We report on an infant with this disorder who had profound humoral and cellular immunologic abnormalities consistent with severe combined immune deficiency (SCID). The infant died at age 2 months of overwhelming cytomegalovirus pneumonia. Kyphomelic dysplasia, as with other short stature/short‐limb skeletal dysplasias, can be associated with immune deficiency and immune function should be investigated when this disorder is identified. © 1995 Wiley‐Liss, Inc.
Apparent Malpuech syndrome: Report on three Brazilian patients with additional signs
Authors: Guion‐Almeida M. L.
Published: June 2005

We report on 3 unrelated Brazilian patients with shortness of stature, hypertelorism, eye anomalies, facial clefting, hearing loss, urogenital abnormalities, omphalocele, “caudal appendage,” and mental retardation. Two patients were born to normal and nonconsanguineous parents and one was born to consanguineous (first cousin) parents (F=1/16). The similarity of our patients with those previously reported by Malpuech et al. [Am J Med Genet 16:475–480, 1983] led us to suggest that they have the same condition. © 1995 Wiley‐Liss, Inc.
Congenital healed cleft lip
Authors: Castilla Eduardo E. , Martínez‐Frías María Luísa
Published: June 2005

Congenital “healed” cleft lip (CHCL) is an unusual anomaly including a paramedian “scar” of the upper lip, which appears as if a typical cleft lip has been corrected in utero. The CHCL is frequently associated with an ipsilateral notch in the vermilion, and “collapsed” nostril.

Twenty‐five CHCL cases are presented, eighteen of which were an isolated malformation found among the 3,950,715 births examined in two similar birth defect registries: ECEMC in Spain and ECLAMC in Latin America.

Like open cleft lip, of which it seems to be a variant, CHCL is most frequently seen among males (14/18 isolated cases), it preferentially affects the left side (10/18 cases), and it segregated together with cleft lip in one family.

The five CHCL cases with other congenital anomalies included: two cases with hydrocephalus, two VACTERL associations, and one atypical oblique facial cleft infant with single umbilical artery.

CHCL may result from a defective fusion of the frontonasal and maxillary processes (before week 7 of embryonic life), or from a spontaneously repaired open cleft lip, later on. In either way, these cases heal with a visible scar, and the pre‐occurrence of CHCL in two families suggests a familial predisposition to this phenomenon. © 1995 Wiley‐Liss, Inc.
Uniparental disomy in congenital disorders: A prospective study
Authors: Lindor Noralane M. , Karnes Pamela S. , Michels Virginia V. , Dewald Gordon W. , Goerss Jean , Jalal Syed , Jenkins Robert B. , Vockley Gerard , Thibodeau Stephen N.
Published: June 2005

Whole chromosome uniparental disomy (UPD) for several different chromosomes has been described in individuals with phenotypes that encompass a broad range of abnormalities. We prospectively searched for UPD in 25 cytogenetically normal individuals who had one or more of the following features: nonsyndromic multiple congenital anomalies, short stature, mental retardation, or dysmorphic findings. Using highly polymorphic microsatellite repeats, biparental inheritance of at least one locus on every chromosome was found in every individual and uniparental inheritance was not detected at any locus. If UPD does exist in this clinical setting, its frequency is less than 13.7% (95% confidence interval). Our data indicate that additional studies will be required to determine the true incidence of UPD in this population. © 1995 Wiley‐Liss, Inc.
Intestinal lymphangiectasia in a patient with Zellweger cerebrohepatorenal syndrome
Authors: Erdem Güliz , Oran Olcay , Kotiloğlu Esin , Kale Gülsev , Topçu Meral , Renda Yavuz
Published: June 2005

Zellweger cerebrohepatorenal syndrome (ZWCHRS) is an autosomal‐recessive disease, characterized by the absence or profound deficiency of peroxisomes. We report a case of ZWCHRS with intestinal lymphangiectasia, observed as an autopsy finding. This combination is previously unreported. © 1995 Wiley‐Liss, Inc.
Radio‐ulnar synostosis, short stature, microcephaly, scoliosis, and mental retardation
Authors: Tsukahara Masato , Matsuo Kiyosato , Furukawa Susumu
Published: June 2005

We report on a 9‐year‐old boy with radioulnar synostosis, short stature, microcephaly, soliosis, and mental retardation. We propose that he has a new syndrome. © 1995 Wiley‐Liss, Inc.
Genetic mapping of the cleidocranial dysplasia (CCD) locus on chromosome band 6p21 to include a microdeletion
Authors: Gelb Bruce D. , Cooper Ed , Shevell Michael , Desnick Robert J.
Published: June 2005

Cleidocranial dysplasia (CCD) is a generalized skeletal dysplasia with autosomal dominant inheritance. Recently, the CCD disease locus was localized to 23 [Mundlos et al., 1995] and 17 cM regions [Feldman et al., 1995], of chromosome band 6p21 by linkage studies of seven affected families. Of note, the 23 cM region contained a microdeletion detected in one family at D6S459, an interval that was excluded in the 17 cM overlapping region. Here, linkage of CCD to 6p21 was independently confirmed with a maximal two‐point LOD score of Z=5.12 with marker D6S452 at θ=0.00. Recombinant events in two affected individuals defined a CCD region of 7 cM from D6S465 to D6S282, which overlapped with the CCD region containing the microdeletion but did not overlap with the 17 cM critical region from D6S282 to D6S291. These results suggest the refined localization of the CCD region to 6 cM spanning markers D6S438 to D6S282, thereby reviving the possibility that the CCD gene lies within the microdeletion at D6S459. © 1995 Wiley‐Liss, Inc.
Syndrome of arachnodactyly, disturbance of cranial ossification, protruding eyes, feeding difficulties, and mental retardation
Authors: Kosztolányi György , Weisenbach János , Méhes Károly
Published: June 2005

We have evaluated an infant with a striking combination of craniofacial anomalies, arachnodactyly, and severe developmental failure. She died at the age of 5 months during a recurrent apneic episode. She also had protruding eyes, downward slant of palpebral fissures, short upturned nose, midface hypoplasia, micrognathia, extreme underdevelopment of the epiglottis, and severe feeding difficulties. The patient closely resembled four other previously reported patients. It is suggested that these five patients represent the same malformation syndrome, a well‐recognizable separate entity. Our patient also had a pericentric inversion of chromosome 10; a possible association of this with the phenotype cannot be excluded. © 1995 Wiley‐Liss, Inc.
Use of decision analysis to evaluate patients' choices of diagnostic prenatal test
Authors: Verp Marion S. , Heckerling Paul S.
Published: June 2005

Women with a family history of a chromosomal or genetic abnormality must weigh several factors in choosing between amniocentesis and chorionic villus sampling. We compared the prenatal test choices of three such women with those of decision analytic models that incorporated their prefernces. Patient preferences were assessed using visual linear rating scales. Threshold analysis was used to determine preference ranges, and stochastic sensitivity analysis to provide confidence levels, for each choice of test. The test choices of patients and decision analytic models agreed in one case, and disagreed in two cases. In one of the latter two cases, stochastic and threshold analyses showed the disagreement to be slight; for small shifts in prefernce differences for first‐vs. second‐trimester diagnosis, or firstvs. second‐trimester therapeutic abortion, patient and decision model would have agreed. In the other, stochastic analysis showed their differences to be large; there were no thresholds for early diagnosis, or for early therapeutic abortion, that would have led to agreement between patient and model. In the two cases in which patient and decision model agreed or slightly disagreed, the patients had made their own choice of prenatal test. In the case in which patient and decision model strongly disagreed, the patient's physician had shared in the choice of test. Decision analysis can be useful in analyzing prenatal test choices based on individual prefernces for pregnancy outcomes. When choices of patients and decision models do not agree, examination of the locus of decision making (patient vs. physician) may help resolve apparent differences. © 1995 Wiley‐Liss, Inc.
Craniomicromelic syndrome: A newly recognized lethal condition with craniosynostosis, distinct facial anomalies, short limbs, and intrauterine growth retardation
Authors: Barr Mason , Heidelberger Kathleen P. , Comstock Christine H.
Published: June 2005

We report on two sisters with an unusual form of craniosynostosis, protruding nasal spine, micrognathia, short limbs, lung hypoplasia, absent or hypoplastic gallbladder, short intestine with ileal distention, hypoplastic uterus, and intrauterine growth retardation. This combination of defects appears to be a newly recognized and probably autosomal recessive disorder. © 1995 Wiley‐Liss, Inc.
Maternal origin of extra haploid set of chromosomes in third trimester triploid fetuses
Authors: Dietzsch Erin , Ramsay Michele , Christianson Arnold L. , Henderson Bertram D. , de Ravel Thomy J. L.
Published: June 2005

Twenty‐six highly polymorphic markers were used to determine the origin of the extra haploid chromosome set in 6 triploid fetuses of type II phenotype. All had reached the third trimester of pregnancy. The extra set was maternal in origin in all cases, supporting previous research indicating longer in utero survival of maternally‐derived triploid fetuses. These findings provide evidence for an instance of genomic imprinting in humans. © 1995 Wiley‐Liss, Inc.
Increased first trimester nuchal translucency as a prenatal manifestation of Smith‐Lemli‐Opitz syndrome
Authors: Hyett Jon A. , Clayton Peter T. , Moscoso Gonzalo , Nicolaides Kypros H.
Published: June 2005

Routine ultrasound examination at 11 weeks of gestation in a woman with no family history of genetic disease demonstrated increased accumulation of fluid in the fetal nuchal region. In view of the association of this defect with chromosomal abnormalities, fetal karyotyping was performed by chorion villus sampling and this demonstrated a normal 46,XY karyotype. Subsequent scans showed resolution of the nuchal fluid, and at the 20‐week scan the fetal genitalia appeared to be female. Fetal blood sampling confirmed a normal male karyotype and fetoscopy confirmed the presence of female external genitalia. The parents elected to terminate the pregnancy, and postmortem findings were indicative of Smith‐Lemli‐Opitz syndrome. This was confirmed by the finding of increased levels of 7‐dehydrocholesterol in cultured skin fibroblasts. © 1995 Wiley‐Liss, Inc.
Detection of a subtle rearrangement of chromosome 22 using molecular techniques
Authors: Biesecker Leslie G. , Rosenberg Marjorie , Dziadzio Laura , Ledbetter David H. , Ning Yi , Sarneso Carmella , Rosenbaum Kenneth
Published: June 2005

Conventional cytogenetics is a useful clinical tool that has a lower limit of sensitivity of 2–5 Mb for detection of duplications of deletions. Because the threshold of clinically significant aneusomy is below this range, there is a need for approaches to improve the sensitivity of the detection of aneusomy. We have implemented a system of screening for subtle unbalanced translocations in children with multiple congenital anomalies of unkonwn cause. Our approach uses subtelomeric microsatellite markers to detect small areas of segmental aneusomy due to unbalanced translocations. Herein we report a patient with severe multiple congenital anomalies and a normal karyotype who was diagnosed by this approach. Microsatellite markers from 41 telomeres were analyzed and were normal with the exception of those on distal chromosome 22. Further analysis with additional microsatellites and fluorescent in in situ hybridization confirmed duplication of 22q13.2‐qter. We conclude that microsatellite screening can detect subtle unbalanced translocations in children with severe anomalies. © 1995 Wiley‐Liss, Inc.
Hemangioma, supraumbilical midline raphé, and coarctation of the aorta with a right aortic arch: Single causal entity?
Authors: Kishnani Priya , Iafolla A. Kimberly , McConkie‐Rosell Allyn , Van Hove Johan L. K. , Kanter Ronald J. , Kahler Stephen G.
Published: June 2005

Most congenital cutaneous hemangiomas are a sporadic occurrence. Hemangiomas have been found in association with coarctation of the aorta and a right aortic arch. A separate association has been noted of midline ventral defects with hemangiomas. We report on a patient with multiple hemangiomas, coarctation of the aorta and a right aortic arch, a supraumbilical midabdominal raphé and sternal cleft. Our patient represents an overlap between these two conditions. Review of the literature identified four additional patients with a similar combination of anomalies. The clinical overlap between these 5 patients suggests that they are variants of the same condition and represent a spectrum of defects that includes hemangiomas, midline ventral defects, aortic arch abnormalities and brain malformation. © 1995 Wiley‐Liss, Inc.
Teebi hypertelorism syndrome: Further observations
Authors: Tsukahara Masato , Uchida Masashi , Shinohara Teruo
Published: June 2005

A new autosomal dominant syndrome resembling craniofrontonasal syndrome was identified by Teebi [1987: Am J Med Genet 28:581‐591]. We report on an additional case of Teebi hypertelorism syndrome. A 6‐year‐old girl presented with brachycephaly, peculiar facial appearance resembling mild frontonasal “dysplasia,” small hands and feet with interdigital webbing. In addition, she had previously undescribed manifestations including ventricular septal defect, lipoma of the occipital area, and hypoplastic left hemisphere of the cerebellum. These seem to expand the phenotype of Teebi hypertelorism syndrome. The proposita's father had mild manifestations of the condition including flat occiput, widow's peak, small ears, bulbous nose, brachydactyly with interdigital webbing, and mild shawl scrotum. © 1995 Wiley‐Liss, Inc.
Penoscrotal transposition and associated anomalies: Report of five new cases and review of the literature
Authors: Parida Saroj K. , Hall Bryan D. , Barton Lorayne , Fujimoto Atsuko
Published: June 2005

We present the largest single series of cases (n = 5) of penoscrotal transposition (PST) with carefully documented nongenitourinary/anal anomalies, none of which fell into categories of known syndromes, associations, sequences or chromosome disorders. Several unexpected anomalies were observed including coloboma of the iris and retina, hydrocephalus, microcephaly, diaphragmatic hernia, tracheo‐esophageal fistula/esophageal atresia and cleft palate. The most frequent anomalies other than PST were renal defects (100%) such as renal agenesis and dysplasia, imperforate anus (60%), central nervous system anomalies (60%) and preaxial upper limb defects (40%). Cardiovascular defects (atrial septal defect, double aortic arch with vascular ring) were noted in only one case. The surviving patients (3/5) had postnatal growth failure and mental retardation. Our 5 PST patients are compared to 16 well‐documented cases from the literature. The overall incidence of various extragenital abnormalities were: renal (90%), mental retarardation (60%), imperforate anus (33%), central nervous system (CNS) anomalies (29%), vertebral defects (29%), preaxial limb defects (24%) and congenital heart disease (19%).

PST is a rare heterogenous anomaly, the detection of which should warrant careful clinical evaluation to rule out other anomalies, especially of the urinary system, gastrointestinal tract, upper limbs, craniofacial region and central nervous system. PST may be a localized field defect involving the genitourinary system; however, the wide variety of more distant defects noted in our series and the literature would raise doubt about that assumption. The high frequency of growth deficiency and mental retardation has also not been given due respect as accompanying problems associated with PST. © 1995 Wiley‐Liss, Inc.
Barriers to carrier testing for adult cystic fibrosis sibs: The importance of not knowing
Authors: Fanos Joanna H. , Johnson John P.
Published: June 2005

Early experience in centers offering population screening for cystic fibrosis (CF) has shown that few of the public are taking advantage of the offer [Miller, 1993: New Scientist 139:6]. There is similar low utilization among adult CF sibs [Fanos and Johnson, 1993: Am J Hum Genet 53:A51]. The purpose of this study was to identify factors motivating or interfering with the pursuit of carrier testing in adult CF sibs. Eighty‐four adult CF sibs and their spouses, drawn from Children's Hospital, Oakland, CA, and Children's Hospital, Boston, MA, were interviewed for about an hour, and qualitative material was coded on various themes. Structural and psychological barriers to the transmission of genetic information were identified: 1) sibs encountered difficulty in obtaining information concerning availability of testing; 2) parental guilt and blame prevents parents from discussing genetic issues with the sib; 3) sibs rarely discuss testing with each other; 4) the CF patient or parent often has difficulty with the implications of the sib seeking carrier testing; 5) family and individual myths about carrier status influence the sib's decision to seek testing; 6) statistical odds have lost meaning in families where the rare has already occurred; 7) the sib fears loss of interpersonal desirability; and 8) carrier status can serve an important function in binding guilt. Remaining unaware of their carrier status may serve significant psychological functions for individuals at risk. © 1995 Wiley‐Liss, Inc.
Autosomal dominant “Opitz” GBBB syndrome due to a 22q11. 2 deletion
Authors: McDonald‐McGinn Donna M. , Driscoll Deborah A. , Bason Lynn , Christensen Katherine , Lynch David , Sullivan Kathleen , Canning Douglas , Zavod William , Quinn Norman , Rome Jonathan , Paris Yvonne , Weinberg Paul , Clark Bernard J. , Emanuel Beverly S. , Zackai Elaine H.
Published: June 2005

We report on a family with autosomal dominant paternally inherited “Optiz” GBBB syndrome and an additional case with findings which have been reported in that syndrome. In each case the propositus presented with a vascular ring. Since a vascular ring may be a sign of a 22q11.2 deletion [Zackai et al., 1995], FISH (fluorescencein situhybridization) studies were performed. These studies demonstrated a 22q11.2 deletion in the 3 affected individuals.

Review of Opitz GBBB syndrome and the 22q11.2 microdeletion syndrome demonstrates significant overlap of manifestations including both facial characteristics and structural anomalies. Based on the phenotypic overlap and the presence of a 22q11.2 deletion in our patients with Opitz GBBB syndrome and the presence of a deletion in a patient with lung hypoplasia, absent pulmonary artery, and long segment trachemoalacia, we propose that, in some cases, the Opitz GBBB syndrome may be due to a 22q11.2 deletion. This enlarges the list of “syndromes” associated with the 22q11.2 deletion, which presently includes most patients with DiGeorge, velocardiofacial, and conotruncal anomaly face syndrome. © 1995 Wiley‐Liss, Inc.
Achondrogenesis type II with polydactyly
Authors: Rittler Monica , Orioli Iêda M.
Published: June 2005

We report on a newborn male infant who presented the typical findings of achondrogenesis type II (Langer‐Saldino), and who also showed postaxial polydactyly on both feet and bilateral microtia. Polydactyly is frequently part of the short‐rib syndromes, but has not been reported in achondrogenesis. The hypothesis of polydactyly as part of a contiguous gene syndrome is discussed. © 1995 Wiley‐Liss, Inc.
Kabuki make‐up (Niikawa‐Kuroki) syndrome in five Spanish children
Authors: Galán‐Gómez E. , Cardesa‐García J. J. , Campo‐Sampedro F. M. , Salamanca‐Maesso C. , Martínez‐Frías M. L. , Frías J. L.
Published: June 2005

We describe 5 Spanish children with Kabuki make‐up syndrome (KMS)—3 females and 2 males—identified in Badajoz, Spain, between 1988 and 1990. All had the characteristic clinical and radiological manifestations of the syndrome. Psychomotor/mental retardation, postnatal growth deficiency, distinctive facial appearance, sagittal vertebral clefts, and dermatoglyphic abnormalities were present in all 5. Congenital heart defects were present in 4 patients. In addition, one had myopia, astigmatism, and bilateral paralysis of the VI cranial nerve. Another had apparent fusion of the hamate and capitate. An additional patient, as well as his mother, had an apparently balanced 15/17 translocation [46,XY,t(15;17) (15q;21q)]. The fact that these patients were ascertained in a catchment area of approximately 250,000 inhabitants and in a relatively limited period of time suggests that the prevalence of the KMS may be higher than previously recognized. © 1995 Wiley‐Liss, Inc.
Short rib‐dysplasia group (with/without polydactyly): Report of a patient suggesting the existence of a continuous spectrum
Authors: Franceschini P. , Guala A. , Vardeu M. P. , Signorile F. , Franceschini D. , Bolgiani M. P.
Published: June 2005

We report on a patient with manifestations typical of Mohr syndrome and of the short rib (polydactyly) syndromes (SR(P)S) Majewski, Verma‐Naumoff, Beemer, and Jeune. It seems possible that the different types of SR(P) syndromes, rather than being distinct conditions, are part of a large disease spectrum. The frequent overlap between orofaciodigital syndromes and SR(P) syndromes may be interpreted as the outcome of deletions of different size within the same chromosome region. © 1995 Wiley‐Liss, Inc.
Inversion duplication of the short arm of chromosome 8: Clinical data on seven patients and review of the literature
Authors: de Die‐Smulders Christine E. M. , Engelen John J. M. , Schrander‐Stumpel Constance T. R. M. , Govaerts Lutgarde C. P. , de Vries Bert , Vles Johannes S. H. , Wagemans Annemiek , Schijns‐Fleuren Suzanne , Gillessen‐Kaesbach Gabriele , Fryns Jean‐Pierre
Published: June 2005

We report on clinical and cytogenetic data on 5 children and 2 adults with a de novo inverted duplication of the short arm of chromosome 8, and we give a review of 26 patients from the literature. The clinical picture in young children is characterized by minor facial anomalies, hypotonia, and severe developmental delay. In older patients the facial traits are less characteristic, spastic paraplegia develops, and severe orthopedic problems are frequent. Psychomotor retardation is always severe‐to‐profound. Duplication of 8p21‐p22 results in a clinically recognizable multiple congenital anomalies/mental retardation (MCA/MR) syndrome. It is shown that in all patients examined, the duplication was accompained by a deletion of the most terminal part of 8p. © 1995 Wiley‐Liss, Inc.
Autosomal‐recessive microcephaly in two siblings, one with normal IQ and both with protruding mandible, small ears, and curved nose
Authors: Rizzo Renata , Pavone Lorenzo
Published: June 2005

We report on 2 sibs with severe microcephaly and unusual associated manifestations. The brother has borderlinehormal intelligence, episodic seizures, clumsiness, and the more severe of facial manifestations; the sister has normal IQ and neither seizures nor behavior abnormalities. Small ears, markedly protruding midface, curved nose, and severe retrognathia are present in both sibs. We postulate that our patients have a “new” form of AR microcephaly, since normal intelligence is not found, nor are the associated findings as pronounced, as in other, more common forms of AR microcephaly (i.e., “microcephalia vera”). © 1995 Wiley‐Liss, Inc.
Partial monosomy of chromosome 1p36.3: Characterization of the critical region and delineation of a syndrome
Authors: Reish Orit , Berry Susan A. , Hirsch Betsy
Published: June 2005

We describe 5 patients ranging in age from 3 to 47 years, with karyotypic abnormalities resulting in monosomy for portion of 1p36.3, microcephaly, mental retardation, prominent forehead, deep‐set eyes, depressed nasal bridge, flat midface, relative prognathism, and abnormal ears. Four patients have small hands and feet. All exhibited selfabusive behavior. Additional findings in some of the patients include brain anomalies, optic atrophy, hearing loss and skeletal deformities. The breakpoints within chromosome 1 were designated at 1p36.31 (3 cases), 1p36.32 (1 case) and 1p36.33 (1 case), Thus, the smallest region of deletion overlap is 1p36.33→1pter. Detection of the abnormal 1 relied on high resolution G‐band analysis. Fluorescence in situ hybridization (FISH) utilizing a DNA probe (Oncor D1Z2) containing the repetitive sequences in distal 1p36, confirmed a deletion of one 1 homologue in all 5 cases. The abnormal 1 resulted from a de novo deletion in only one patient. The remaining patients were either confirmed (3 cases) or suspected (1 case) to have unbalanced translocations. Despite the additional genetic imbalance present in these four cases, monosomy of 1p36.33 appears to be responsible for a specific clinical phenotype. Characterization of this phenotype should assist in the clinical diagnosis of this chromosome abnormality. © 1995 Wiley‐Liss, Inc.
Analysis of clinical variation seen in patients with 18q terminal deletions
Authors: Strathdee Gordon , Zackai Elaine H. , Shapiro Ray , Kamholz John , Overhauser Joan
Published: June 2005

Twenty‐six patients with deletions of 18q were analyzed at the clinical and molecular levels in an attempt to delineate regions of chromosome 18 important to the 18q– syndrome phenotype. Molecular cytogenetic analysis was carried out using fluorescence in situ hybridization (FISH), and deletions ranging from 18q21.1–qter to 18q22.3–qter were detected. The parental origin of the deletions was determined by the analysis of inheritance of microsatellite markers. No correlation between size, parental origin, or severity of the resulting phenotype was found. The results suggest that a critical region for the 18q– syndrome lies in the most distal portion of 18q and that it confers susceptibility for the various clinical manifestations of the 18q– syndrome when present in one copy. © 1995 Wiley‐Liss, Inc.
Linkage between stature and a region on chromosome 20 and analysis of a candidate gene, bone morphogenetic protein 2
Authors: Thompson D. Bruce , Ossowski Victoria , Janssen Rachel C. , Knowler William C. , Bogardus Clifton
Published: June 2005

Sib‐pair linkage analysis of the quantitative trait, stature, in over 500 Pima Indians indicates that a genetic determinant of governing stature is located on chromosome 20. Analysis of 10 short tandem repeat polymorphisms localized this linkage to a 3.2cM region that includes D20S98 and D20S66. Using all possible sib‐pair combinations, linkage was detected to both stature (P = 0.0001) and to leg length (P = 0.001), but not to sitting height. Single‐strand conformational polymorphism analysis of exon 3 of the bone morphogenetic protein 2 (BMP2) gene, a candidate gene in this region, in genomic DNA of 20 of the tallest and 20 of the shortest individuals did not show any consistent differences associated with leg length or height. Sequence analysis of the region encoding the mature protein revealed a single nucleotide substitution, a T to G transversion, not detected by single‐strand conformational polymorphism (SSCP) analysis. This transversion results in a conservative amino acid substitution of glycine for valine at codon 80 of BMP2. The frequency of this allele was 0.23 in the sample. No significant differences in height were noted in persons carrying either allele. This indicates that this structural alteration in the mature BMP2 protein does not contribute to the differences in stature observed in the Pima Indians, nor is this structural change in the mature protein likely to be responsible for the linkage observed with stature on chromosome 20. © 1995 Wiley‐Liss, Inc.

This article is a U.S. Government work and, as such, is in the public domain in the United States of America.