bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid molecular cytogenetic analysis of X‐chromosomal microdeletions: Fluorescence in situ hybridization (FISH) for complex glycerol kinase deficiency
Authors: Worley K. C. , Lindsay E. A. , Bailey W. , Wise J. , McCabe E. R. B. , Baldini A.
Published: June 2005

Diagnosis of X‐chromosomal microdeletions has relied upon the traditional methods of Southern blotting and DNA amplification, with carrier identification requiring timeconsuming and unreliable dosage calculations. In this report, we describe rapid molecular cytogenetic identification of deleted DNA in affected males with the Xp21 contiguous gene syndrome (complex glycerol kinase deficiency, CGKD) and female carriers for this disorder.

CGKD deletions involve the genes for glycerol kinase, Duchenne muscular dystrophy, and/or adrenal hypoplasia congenita. We report an improved method for diagnosis of deletions in individuals with CGKD and for identification of female carriers within their families, using fluorescence in situ hybridization (FISH) with a cosmid marker (cosmid 35) within the glycerol kinase gene. When used in combination with an Xq control probe, affected males demonstrate a single signal from the control probe, while female carriers demonstrate a normal chromosome with two signals, as well as a deleted chromosome with a single signal from the control probe. FISH analysis for CGKD provides the advantages of speed and accuracy for evaluation of submicroscopic X‐chromosomal deletions, particularly in identification of female carriers. In addition to improving carrier evaluation, FISH will make prenatal diagnosis of CGKD more readily available. © 1995 Wiley‐Liss, Inc.
Removing the shadow of the law from the debate about genetic testing of children
Authors: Clayton Ellen Wright
Published: June 2005

When physicians view efforts to obtain genetic testing for children as unwise or contrary to the children's interests, they face difficult problems both of ethics and of communicating with the parents. Contrary to the suggestions of some, the law has little to say about how physicians resolve these dilemmas. Parents do not have a constitutionally protected right to demand that unwilling physicians perform these tests. In addition, there is little risk of liability for damages unless the child suffers physical harm as a result of the physician's refusal to do the test. The debate about genetic testing of children needs to take place with a clear understanding of the law's limited impact. © 1995 Wiley‐Liss, Inc.
Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q
Authors: Koiffmann Célia P. , Gonzalez Claudette H. , Vianna‐Morgante Angela M. , Kim Chong A. , Odone‐Filho Vicente , Wajntal Anita
Published: June 2005

Deletion 11q23→qter and duplication 12q23→qter are described in a boy with neuroblastoma, multiple congenital anomalies, and mental retardation. The patient has clinical manifestations of 11q deletion and 12q duplication syndromes. The possible involvement of the segment 11q23→24 in the cause of the neuroblastoma is discussed. © 1995 Wiley‐Liss, Inc.
Are we all of one mind? Clinicians' and patients' opinions regarding the development of a service protocol for predictive testing for Huntington disease
Authors: Copley Tobin T. , Wiggins Sandi , Dufrasne Suzanne , Bloch Maurice , Adam Shelin , McKellin William , Hayden Michael R.
Published: June 2005

There are currently different research programs in place to assess the effects of predictive testing for a few late‐onset disorders, including Huntington disease (HD) and familial cancers. Prior to providing predictive testing as a service, we sought the views of both the patients and the clinicians as to the importance and value of different items in a research protocol for HD. We mailed questionnaires to 41 clinicians and 351 at‐risk patients who had participated in the research protocol, to solicit their opinions on the relative importance of various components of the HD predictive testing research protocol. Completed questionnaires were received from 256 patients (73%) and 33 clinicians (80%). Most participants (96%) were satisfied with the program, and <3% of persons receiving a modification of risk felt that predictive testing had impaired their quality of life. While there was consensus on the importance of most components of the protocol, significantly more clinicians than patients (97% vs. 72%; P =0.02) felt it was essential to keep written material about HD as part of a service protocol. More patients than clinicians (83% vs. 27%) considered it essential to have 24‐hr contact numbers following disclosure of test results (P < 0.0001). Patients also felt more strongly about the importance of counseling about technical aspects of predictive testing (84% vs. 77%; P < 0.02), and about having a support person attend counselling sessions with the patient (62% vs. 48%; P = 0.04). Nearly 25% of participants indicated that they would not want their general practioner routinely involved in the predictive testing program. These findings have influenced the development of our service protocol, and they underscore the importance of involving both providers and consumers of predictive testing in the development of a service protocol for genetic testing. © 1995 Wiley‐Liss, Inc.
Pelizaeus‐Merzbacher disease caused by a de novo mutation that originated in exon 2 of the maternal great‐grandfather of the propositus
Authors: Pratt Victoria M. , Boyadjiev Simon , Green Kathryn , Hodes M. E. , Dlouhy Stephen R.
Published: June 2005

Pelizaeus‐Merzbacher disease (PMD) is an X‐linked dysmyelinating disorder of the central nervous system. Many cases of PMD can be attributed to defects in the proteolipid protein gene (PLP). To date, with one exception, each family has had either no or a unique mutation in one of the seven exons of PLP. We describe a new missense mutation in exon 2 of the PLP gene of an affected individual. This mutation codes for Ile instead of Thr at codon 42. The point mutation originated in the X chromosome of the maternal great‐grandfather of the propositus. This was determined from the pattern of inheritance of the AhaII polymorphism and a series of microsatellite markers that are localized near PLP at Xq22. © 1995 Wiley‐Liss, Inc.
Trisomy 1q42→qter in a sister and brother: Further delineation of the “trisomy 1q42→qter Syndrome”
Authors: Verschuuren‐Bemelmans Corien C. , Leegte Beike , Hodenius Thea M. J. , Cobben Jan M.
Published: June 2005

We report on a 22‐year‐old woman and her 21‐year‐old brother with mild mental retardation, long face, prominent forehead, retrognathia, and (relative) macrocephaly. At birth they were small for date, their length is now below the 10th centile. Chromosome analysis demonstrated a nearly pure trisomy 1q42→qter in both patients due to unbalanced segregation of a paternal reciprocal balanced translocation 46,XY,t(1;15) (q42;p11). This is the second report of a nearly pure trisomy 1q42→qter.

When comparing the manifestations of our patients with those of other reported cases we conclude that the most characteristic clinical manifestations of this syndrome are macrocephaly, prominent forehead, micro/retrognathia, large fontanelle, intrauterine growth retardation, postnatal growth retardation, and mental retardation. © 1995 Wiley‐Liss, Inc.
Monozygotic twins discordant for the russell‐silver syndrome
Authors: Bailey Wendy , Popovich Bradley , Jones Kenneth Lee
Published: June 2005

Russell‐Silver syndrome (RSS) is a pattern of malformation characterized by intrauterine and postnatal growth retardation, limb asymmetry, triangular face, and hypospadias. We report on a patient, from a triplet pregnancy, who was one of identical male twins discordant for RSS. R.B. was a 710‐g male born at 33 weeks of gestation, with hypospadias, chordee, and undescended testes. He had a normal 46,XY karyotype and no renal abnormalities. Female triplet A weighed 1,843 g, and male triplet B weighed 1,920 g. Both had normal physical findings and neonatal period. R.B. was first seen by us at age 6 7/12 years with short stature, triangular and asymmetric face, lower limb length discrepancy, and surgically repaired genital anomalies. Growth hormone testing results were normal. At age 8 7/12 years the brothers appeared physically identical except for size, with a height differential of 114.25 vs. 121.5 cm. Testing to establish biological zygosity was performed using VNTR (variable number tandem repeat) DNA probes YNH24 (D2S44), CMM101 (D14S13), EFD52 (D17S26), TBQ7 (D10S28), and 3′HVR (D16S85), PCR loci MCT118 (D1S80), and HLA‐DQα. These data indicate a >99.99% probability of triplets B and C being monozygotic twins. While most occurrences of RSS are sporadic, familial cases suggesting autosomal dominance have been reported. Three other cases of probable monozygotic twins with RSS have been described. The significance of this confirmation of discordance in determining the cause of RSS is discussed. © 1995 Wiley‐Liss, Inc.
Alopecia/mental retardation syndrome
Authors: Hannig Vickie L. , Tiller George E.
Published: June 2005

We report on an African‐American patient with alopecia universalis, microcephaly, hypogonadism, and mental and growth retardation, and compare his phenotype to others with recessive alopecia/mental retardation syndromes in the literature. Our patient represents the first case reported from nonconsanguineous African‐American parents. © 1995 Wiley‐Liss, Inc.
Fibrillin abnormalities and prognosis in marfan syndrome and related disorders
Authors: Aoyama Takeshi , Francke Uta , Gasner Cheryll , Furthmayr Heinz
Published: June 2005

Marfan syndrome (MFS), a multisystem autosomal‐dominant disorder, is characterized by mutations of the fibrillin‐1 (FBN1) gene and by abnormal patterns of synthesis, secretion, and matrix deposition of the fibrillin protein. To determine the sensitivity and specificity of fibrillin protein abnormalities in the diagnosis of MFS, we studied dermal fibroblasts from 57 patients with classical MFS, 15 with equivocal MFS, 8 with single‐organ manifestations, and 16 with other connective tissue disorders including homocystinuria and Ehlers‐Danlos syndrome. Abnormal fibrillin metabolism was identified in 70 samples that were classified into four different groups based on quantitation of fibrillin synthesis and matrix deposition. Significant correlations were found for phenotypic features including arachnodactyly, striae distensae, cardiovascular manifestations, and fibrillin groups II and IV, which included 70% of the MFS patients. In addition, these two groups were associated with shortened “event‐free” survival and more severe cardiovascular complications than groups I and III. The latter included most of the equivocal MFS/single manifestation patients with fibrillin abnormalities. Our results indicate that fibrillin defects at the protein level per se are not specific for MFS, but that the drastically reduced fibrillin deposition, caused by a dominant‐negative effect of abnormal fibrillin molecules in individuals defined as groups II and IV, is of prognostic and possibly diagnostic significance. © 1995 Wiley‐Liss, Inc.
Characterization of genetic deletions in becker muscular dystrophy using monoclonal antibodies against a deletion‐prone region of dystrophin
Authors: Thanh Le Thiet , Man Nguyen Thi , Hori S. , Sewry C. A. , Dubowitz V. , Morris G. E.
Published: June 2005

We have produced a new panel of 20 monoclonal antibodies (mAbs) against a region of the dystrophin protein corresponding to a deletion‐prone region of the Duchenne muscular dystrophy gene (exons 45–50). We show that immuno‐histochemistry or Western blotting with these “exon‐specific” mAbs can provide a valuable addition to Southern blotting or PCR methods for the accurate identification of genetic deletions in Becker muscular dystrophy patients. The antibodies were mapped to the following exons: exon 45 (2 mAbs), exon 46 (6), exon 47 (1), exons 47/48 (4), exons 48–50 (6), and exon 50 (1). PCR amplification of single exons or groups of exons was used both to produce specific dystrophin immunogens and to map the mAbs obtained. PCR‐mediated mutagenesis was also used to identify regions of dystrophin important for mAb binding. Because the mAbs can be used to characterize the dystrophin produced by individual muscle fibres, they will also be useful for studying “revertant” fibres in Duchenne muscle and for monitoring the results of myoblast therapy trials in MD patients with deletions in this region of the dystrophin gene. © 1995 Wiley‐Liss, Inc.
Omphalocele and gastroschisis in Europe: A survey of 3 million births 1980–1990
Authors: Calzolari E. , Bianchi F. , Dolk H. , Milan M.
Published: June 2005

A total of 732 cases of omphalocele and 274 cases of gastroschisis was registered in 21 regional registers in Europe (EUROCAT registers) during the period 1980–1990. The total prevalence rates were 2.52 per 10,000 for omphalocele and 0.94 per 10,000 for gastroschisis. There was significant heterogeneity in total prevalence rates among regions for omphalocele. Consistently higher than average total prevalence rates of omphalocele were found in the five centers of the British Isles. This was in large part linked to the association between omphalocele and neural tube defects. A significant female excess among the cases of omphalocele associated with neural tube defects, in comparison with an insignificant male excess for other cases of omphalocele, was observed. Geographical differences in the total prevalence of gastroschisis are partly explained by differences in maternal age distributions in the populations surveyed. Omphalocele was an isolated malformation in 46% of cases; gastroschisis was isolated in 79% of cases. The average birthweight and gestational age of both isolated and multiply malformed cases of both omphalocele and gastroschisis were low, especially for multiply malformed cases, and to a greater extent for isolated gastroschisis than for isolated omphalocele. Prenatal diagnosis leading to termination of pregnancy was reported in 33.2% of omphalocele and in 26.5% of gastroschisis cases, demonstrating the considerable impact of current prenatal screening programs. On the basis of clinical manifestations, epidemiologic characteristics, and the presence and type of additional malformations, omphalocele and gastroschisis can be considered heterogeneous conditions. © 1995 Wiley‐Liss, Inc.
Duchenne muscular dystrophy and idiopathic hyperCKemia segregating in a family
Authors: Frydman Moshe , Straussberg Rachel , Shomrat Ruth , Goebel Hans , Legum Cyril , Shiloh Yossi
Published: June 2005

A 7‐month‐old boy with gross motor delay and failure to thrive presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization an electrocardiographic conversion to a Wolff‐Parkinson‐White type 1 (WPW) pattern took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated creatine kinase (CK) serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analysis, which documented a deletion corresponding to cDNA probe 1‐2a in the dystrophin gene, in the propositus and in an affected male cousin of his mother. “Idiopathic” hyperCKemia was found in the propositus, his father, and 5 of his relatives. We suggest that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of the maternal DMD gene and of a paternal gene, causing hyperCKemia. © 1995 Wiley‐Liss, Inc.
Hereditary spherocytic anemia with deletion of the short arm of chromosome 8
Authors: Okamoto Nobuhiko , Wada Yoshinao , Nakamura Yoich , Nakayama Masahiro , Chiyo Hideaki , Murayama Kikuno , Inoue Takahumi , Kanzaki Akio , Yawata Yoshihito , Hirono Akira , Miwa Shiro
Published: June 2005

We describe a 30‐month‐old boy with multiple anomalies and mental retardation with hereditary spherocytic anemia. His karyotype was 46,XY,del(8)(p11.23p21.1). Genes for ankyrin and glutathione reductase (GSR) were localized to chromosome areas 8p11.2 and 8p21.1, respectively. Six patients with spherocytic anemia and interstitial deletion of 8p– have been reported. In these patients, severe mental retardation and multiple anomalies are common findings. This is a new contiguous gene syndrome. Lux et al. [1990: Nature 345:736–739] established that ankyrin deficiency and associated deficiencies of spectrin and protein 4.2 were responsible for spherocytosis in this syndrome. We reviewed the manifestations of this syndrome. Patients with spherocytic anemia and multiple congenital anomalies should be investigated by high‐resolution chromosomal means to differentiate this syndrome. © 1995 Wiley‐Liss, Inc.
Prenatal exposure to phenytoin, facial development, and a possible role for vitamin K
Authors: Howe Andrew M. , Lipson Anthony H. , Sheffield Leslie J. , Haan Eric A. , Halliday Jane L. , Jenson Fred , David David J. , Webster William S.
Published: June 2005

Ten patients with maxillonasal hypoplasia (Binder “syndrome”), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant‐induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at‐risk pregnacies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time. © 1995 Wiley‐Liss, Inc.
Galloway‐Mowat syndrome in Taiwan
Authors: Hou Jai‐Woei , Wang Tso‐Ren
Published: June 2005

We report on two Chinese female infants with multiple congenital anomalies: microcephaly, apparent porencephaly or encephalomalacia, developmental delay, minor facial anomalies, and contractural arachnodactyly. In the first patient, focal glomerulosclerosis was diagnosed histologically by percutaneous renal biopsy due to proteinuria with hematuria. Congenital hypothyrodism presenting with markedly low T3 and T4 was also noted. She died at age 5 months. The second patient had a very similar condition but less severe brain and kidney malformations. A variant of Galloway‐Mowat syndrome is suspected. © 1995 Wiley‐Liss, Inc.
Recurrent lambdoid synostosis within two families
Authors: Fryburg Julie S. , Hwang Vivian , Lin Kant Y.
Published: June 2005

We report on 2 families with multiple members who have proven or suspected lambdoid craniosynostosis. In one family the lambdoid suture was unilaterally involved in one sib, and bilaterally in the other. In the second family the propositus had unilateral lambdoid synostosis and his twin sisters each had bilateral lambdoid synostosis. Both families had another distant relative, a maternal grandmother in the first and paternal uncle in the second, who were also reported to have posterior plagiocephaly. We report these families as evidence for genetic transmission of a craniosynostotic trait which has only been rarely reported previously. © 1995 Wiley‐Liss, Inc.
Absence of λ immunoglobulin sequences on the supernumerary chromosome of the “cat eye” syndrome
Authors: Hough Christine A. , White Bradley N. , Holden Jeanette J. A.
Published: June 2005

The supernumerary bisatellited chromosome causing the “cat eye” syndrome (CES) is of chromosome 22 origin and consists of an inverted duplication of the 22pter→22q11.2 region. To determine the extent of involvement of band q11.2 on the bisatellited chromosome, copy number assessment of sequences homologous to cloned λ immunoglobulin (λ Ig) gene region probes was carried out on DNA from individuals with CES using densitometric analysis of Southern blots. None of the 10 λ Ig sequences studied was found in increased copy number in DNA from any of the 10 CES individuals tested, indicating that these sequences are not present on the supernumerary chromosome. The breakpoints involved in the generation of the bisatellited supernumerary chromosome associated with CES are therefore proximal to the λ Ig gene region. © 1995 Wiley‐Liss, Inc.
Four new cases of inverted terminal duplication: A modified hypothesis of mechanism of origin
Authors: Hoo Joe J. , Chao Margaret , Szego Katarina , Rauer Mary , Echiverri Susan C. , Harris Catherine
Published: June 2005

We present 4 recently diagnosed cases of inverted tandem duplication with involvement of the respective terminal band. Based on these 4 cases and review of the literature, the term “inverted terminal duplication” is proposed to designate specifically the type of inverted tandem duplication which involves the terminal band. A modification of the previous hypothesis of mechanism of origin is advanced. It is speculated further that a telomeric deletion of a meiotic chromosome followed by a U‐type reunion of the chromatids, considered to be the first steps of the proposed mechanism of origin, may not be a rare gonadal event. © 1995 Wiley‐Liss, Inc.
Transient leukemia with trisomy 21: Description of a case and review of the literature
Authors: Bhatt Sucheta , Schreck Rhona , Graham John M. , Korenberg Julie R. , Hurvitz Carole G. , Fischel‐Ghodsian Nathan
Published: June 2005

Transient myeloproliferative disease (TMD) is often associated with a trisomy 21 cell line, but it is not always associated with clinical signs of Down syndrome. We report on a phenotypically normal newborn boy who presented with a high white blood cell count, undifferentiated blasts, and cutaneous leukemic infiltrates and compare this patient with the literature on TMD and trisomy 21. Chromosome analysis of bone marrow, and subsequently of skin fibroblasts, documented constitutional mosaicism for trisomy 21. A decrease in the frequency of blast cells paralleled a decrease in cells demonstrating trisomy 21 in hematopietic tissues, and a complete clinical recovery was seen without the use of chemotherapy. Recognition of this transient form of congenital leukemia is important to prevent the unnecessary use of toxic chemotherapeutic agents in such patients. © 1995 Wiley‐Liss, Inc.
Sex, neural tube defects, and multisite closure of the human neural tube
Authors: Seller Mary J.
Published: June 2005

While neural tube defects (NTD) overall have a female sex bias, this does not apply to all sites along the neuraxis. The findings regarding sex and NTD in a series of midtrimester fetuses are reviewed, and then analysed in terms of the recent hypothesis that during embryogenesis of the human neural tube there are multiple closure sites, rather than a single zipping up process. Females more often than males tend to have craniorachischisis, spina bifida involving the thorax, the holoacrania form of anencephaly, anencephaly and cervical spina bifida and encephalocoeles, while males more often than females have spina bifida affecting the lower spine. Meroacrania occurs equally in both sexes. Other sources indicate that there is a male bias in frontoethmoidal encephalocoeles. Since sex seems to be a factor that is differentially associated with lack of closure of specific areas of the neural tube, it would seem to support the notion that there are multiple closure sites in the human neural tube. However, no association was found between a particular sex and either the type of NTD which have an isolated abnormality or those NTD associated with developmental abnormalities of other body systems. © 1995 Wiley‐Liss, Inc.
“New” ectodermal dysplasia with mental retardation and syndactyly
Authors: Ilyina Helena G. , Amoashy Dmitry S. , Grygory Helena A.
Published: June 2005

We describe a girl with an unusual form of ectodermal dysplasia. She was mildly mentally retarded, had normal height, weight, and head circumference, a large scalp defect, a peculiar face with large palpebral fisures, a broad nasal bridge and constantly open mouth, abnormally‐modeled ears, syndactyly of fingers/toes, mild hypohidrosis, and severe onychogryposis. Her hair was short, abundant, and stiff, her eyebrows were sparse, and her skin was dry. Analysis of the literature showed that this type of association of ectodermal dysplasia and other defects has not been previously described. © 1995 Wiley‐Liss, Inc.
Hypoglycemia in Coffin‐Siris syndrome
Authors: Imaizumi Kiyoshi , Nakamura Mihoko , Masuno Mitsuo , Makita Yoshio , Kuroki Yoshikazu
Published: June 2005

We describe a further patient with the Coffin‐Siris syndrome who presented at 4 months with recurrent hypoglycemia attacks. Detailed examination was undertaken at 7 months but the cause of hypoglycemia was not detected. Hypoglycemia seems to be a previously undescribed finding in the Coffin‐Siris syndrome. ©1995 Wiley‐Liss, Inc.
Agonadism in two sisters with XY gonosomal constitution, mental retardation, short stature, severely retarded bone age, and multiple extragenital malformations: A new autosomal recessive syndrome
Authors: Kennerknecht Ingo , von Saurma Petra , Brenner Rolf , Just Walter , Barbi Gotthold , Sorgo Wolfgang , Heinze Eberhard , Wolf Alfred S. , Schneider Volker , Günther Klaus‐Peter , Teller Walter M. , Vogel Walther
Published: June 2005

We report on 12‐ and 14‐year‐old sisters with a 46,XY chromosome constitution, normal female external genitalia, and absence of gonadal tissue. Except for omphalocele, right renal agenesis and malrotation of the colon in the elder sister, the internal organs were normal. Both were mentally retarded, of short stature, and had extremely retarded bone age. In addition, they had an almost identical pattern of minor anomalies: peculiar face, hypodontia, short neck, inverted nipples, thoracolumbar scoliosis, “dysplastic” hips, partial clino‐/syndactyly of toes.

The occurrence of a basically similar set of malformations in two sisters and the first cousin consanguinity of the parents suggests autosomal recessive inheritance. The conserved region of the SRY gene ([high mobility group] HMG box) was sequenced in the elder sib and was normal.

No consistent malformations are observed at present in agonadal patients. This supports the idea that several autosomal genes have the potential of influencing the sequence of events of sex determination. © 1995 Wiley‐Liss, Inc.
Distal deletion of chromosome 13 in a child with the “Opitz” GBBB syndrome
Authors: Urioste Miguel , Arroyo Ignacio , Villa Amelia , Lorda‐Sánchez Isabel , Barrio Raquel , López‐Cuesta María‐Jesús , Rueda Javier
Published: June 2005

We describe a patient who had craniofacial and genitourinary abnormalities, swallowing difficulties, esophageal dysfunction, hypotonia and moderate developmental delay, and who also had a terminal deletion of chromosome 13 (q32.3qter). This MCA pattern strongly suggests the Opitz GBBB syndrome. The deletion of chromosome 13 was interpreted as terminal with a breakpoint at 13q32.3. Coagulation factors VII and X located in 13q34, were markedly reduced in the propositus.

Although there is some clinical overlap between patients with terminal deletion of 13q and those with the Opitz GBBB syndrome, our patient manifests a whole pattern of abnormalities characteristic of the latter disorder. The concurrence of the Opitz GBBB syndrome and the chromosome abnormality in our patient could be due to chance or, be becuase a gene for the Opitz GBBB syndrome is located at the tip of 13q. © 1995 Wiley‐Liss, Inc.
X‐linked ichthyosis without STS deficiency: Clinical, genetical, and molecular studies
Authors: Robledo Renato , Melis Paola , Schillinger Erika , Casciano Ida , Balazs Ivan , Rinaldi Antoniettina , Siniscalco Marcello , Filippi Giorgio
Published: June 2005

We report on a Sardinian pedigree with congential ichthyosis associated with normal levels of steroid sulfatase and a normal molecular pattern, as detectable with a cDNA probe for the steroid sulfatase (STS) gene. Though the pattern of transmission of the disease is consistent with X‐linked recessive inheritance, this form of ichthyosis was found to segregate independently of genetic polymorphisms detected by probes of the region Xp22.3, where the STS locus has been mapped. The search for close genetic linkages with other polymorphic markers scattered along the entire X chromosome has so far been fruitless. For the time being, the main conclusion derived from these data is that STS deficiency is not a sine qua non for X‐linked ichthyosis which may also result from a mutational event at an X‐chromosomal site genetically unlinked to the STS locus. © 1995 Wiley‐Liss, Inc.
Hemifacial hyperplasia with meningeal involvement: A variant of proteus syndrome?
Authors: Haramoto Ushio , Kobayashi Seiichiro , Ohmori Kitaro
Published: June 2005

We report on a sporadic case of hemifacial hamartomatous hyperplasia. The patient is male, and has sebaceous nevus‐like skin change, subcutaneous lipomatous mass, cranial bone hyperplasia, and bony change of meninges. His lesion involves the anterior half of the face and cranial base, and, medially, is delimited by the midline. No case has been found identical to this in the literature, particularly with respect to the unusual meningeal lesion. However, without this meningeal lesion the rest of the manifestations are not uncommon in Proteus syndrome. Also, this case may be an indication of somatic mosaicism, lethal in its nonmosaic state. Thus, this case may be thought of as a variant of Proteus syndrome. © 1995 Wiley‐Liss, Inc.
Molecular analysis of the Duchenne muscular dystrophy gene in Spanish individuals: Deletion detection and familial diagnosis
Authors: Patiño Ana , Narbona Juan , García‐Delgado Marina
Published: June 2005

Deletion studies were performed in 26 Duchenne muscular dystrophy (DMD) patients through amplification of nine different exons by multiplex polymerase chain reaction (PCR). DNA from paraffin‐embedded muscle biopsies was analyzed in 12 of the 26 patients studied. Optimization of this technique is of great utility because it enables analysis of material stored in pathology archives. PCR deletion detection, useful in DMD‐affected boys, is problematic in determining the carrier state in female relatives. For this reason, to perform familial linkage diagnosis, we made use of a dinucleotide repeat polymorphism (STRP, or short tandem repeat polymorphism) located in intron 49 of the gene. We designed a new pair of primers that enabled the detection of 22 different alleles in relatives in the 14 DMD families studied. The use of this marker allowed familial diagnosis in 11 of the 14 DMD families and detection of de novo deletions in 3 of the probands. © 1995 Wiley‐Liss, Inc.
Familial partial duplication (1)(p21p31)
Authors: Hoechstetter Leah , Soukup Shirley , Schorry Elizabeth K.
Published: June 2005

A partial duplication (1)(p21p31), resulting from a maternal direct insertion (13,1) (q22p21p31), was found in a 30‐year‐old woman with mental retardation, cleft palate, and multiple minor anomalies. Two other affected and deceased relatives were presumed to have the same chromosome imbalance. Duplication 1p cases are reviewed. © 1995 Wiley‐Liss, Inc.
Cardiac malformation in two infants with hypochondrogenesis
Authors: Potocki Lorraine , Abuelo Dianne N. , Oyer Calvin E.
Published: June 2005

Autopsy records from the Women and Infants' Hospital from January 1974 through January 1994 were reviewed to identify cardiac malformations in the presence of skeletal dysplasia. Of 24 cases of lethal fetal or neonatal osteochondrodysplasias, 4 were given diagnoses in which disorders of type II collagen are regarded as causative. These 4 were categorized in the spondyloepiphyseal dysplasia (SED) spectrum of disorders; specifically two patients with hypochondrogenesis and two with spondyloepiphyseal dysplasia congenita were identified. Defects in cardiac septation were noted in the 2 patients with hypochondrogenesis. No cardiovascular abnormalities were present in the remaining cases, which included thanatophoric dysplasia, osteogenesis imperfecta, and asphyxiating thoracic dystrophy.

Although cardiovascular malformations have been described in other types of osteochondrodysplasias, e.g., short rib polydactyly syndrome type II and chondroectodermal (Ellis van Creveld) dysplasia, congenital heart disease has not been described in hypochondrogenesis. Type II collagen, which has been found to be abnormal in some patients with hypochondrogenesis, is considered to have a limited tissue distribution, and has not been detected as yet in human myocardium. The findings presented here suggest that type II collagen may function in human cardiogenesis. © 1995 Wiley‐Liss, Inc.
Infantile lethal variant of Simpson‐Golabi‐Behmel syndrome associated with hydrops fetalis
Authors: Terespolsky D. , Farrell S. A. , Siegel‐Bartelt J. , Weksberg R.
Published: June 2005

Simpson‐Golabi Behmel syndrome (SGBS) is an X‐linked disorder characterized by pre‐ and postnatal macrosomia, minor facial anomalies, and variable visceral, skeletal, and neurological abnormalities. Since its first description by Simpson et al. [1975: BD:OA XI(2):18–24], a wide clinical range of cases has been reported. There is great variability in severity, ranging from a mild form associated with long‐term survival to an early lethal form with multiple congenital anomalies and severe mental retardation. In 8 reported families, affected individuals died in infancy.

Here we present 4 maternally related, male cousins with a severe variant of SGBS. One of these males was aborted therapeutically at 19 weeks of gestation following the detection of multicystic kidneys on ultrasound. The 3 liveborn males were hydropic at birth with a combination of craniofacial anomalies including macrocephaly; apparently low‐set, posteriorly angulated ears; hypertelorism; short, broad nose with anteverted nares; large mouth with thin upper vermilion border; prominent philtrum; high‐arched or cleft palate; short neck; redundant skin; hypoplastic nails; skeletal defects involving upper and lower limbs; gastrointestinal and genitourinary anomalies. All 3 patients were hypotonic and neurologically impaired from birth. With the exception of a trilobate left lung in one patient, the cardiorespiratory system was structurally normal. All patients died within the first 8 weeks of life of multiple complications including pneumonia and sepsis.

Two SGBS kindreds, with moderate expression of the condition, have been mapped to Xq27. It is not known whether severe, familial cases, such as ours, are genetically distinct from and map to another locus. Final resolution of the genetic basis of the phenotypic variability in SGBS must await cloning and mutation analysis of the SGBS gene(s). © 1995 Wiley‐Liss, Inc.
Fryns syndrome survivors and neurologic outcome
Authors: Van Hove Johan L. K. , Spiridigliozzi Gail A. , Heinz Ralph , McConkie‐Rosell Allyn , Iafolla A. Kimberly , Kahler Stephen G.
Published: June 2005

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome characterized by diaphragmatic hernia, unusual facies, and distal limb hypoplasia. It was first reported as a lethal condition. We report on a three‐year‐old survivor with Fryns syndrome, and provide a review on the outcome of other survivors. Patients who survive the neonatal period represent 14% of reported cases. Characteristics of survivors include less frequent diaphragmatic hernia and milder lung hypoplasia, absence of complex cardiac malformation, and neurologic impairment. Multiple central nervous system abnormalities have been reported in Fryns syndrome, including agenesis of the corpus callosum, Dandy‐Walker abnormality, cerebellar heterotopias, cerebellar hypoplasia, enlarged ventricles, and hypoplasia of the olfactory bulbs. Our patient exhibited profound mental retardation. He had malformations of gyration and sulcation, particularly around the central sulcus, and hypoplastic optic tracts beyond the optic chiasm. Understanding of long‐term outcome of survivors is important for counseling of families with Fryns syndrome. Careful brain examination is advised; however, a normal radiological brain examination does not preclude developmental delay. The spectrum of individual outcome and of associated anomalies indicates that individual evaluation, imaging for structural brain malformation, is strongly advised. © 1995 Wiley‐Liss, Inc.
Mirror image duplication of the hands and feet: Report of a sporadic case with multiple congenital anomalies
Authors: Hersh J. H. , Cruz T. V. Dela , Pietrantoni M. , von Drasek‐Ascher G. , Turnquest M. A. , Yacoub O. A. , Joyce M. R.
Published: June 2005

Mirror image duplication of the hands and feet is a rare entity. Based on 3 previous reports, findings include nasal abnormalities, dimelia of ulna and fibula, tibial hypoplasia and mirror image duplication of hands and feet. We report on a sporadic case in which mirror image duplication was associated with multiple congenital anomalies. Although these cases may represent variable expression of the same dominantly transmitted complex polysyndactyly syndrome, it is possible that mirror image duplication of the hands and feet is a manifestation common to a number of distinct clinical entities. During limb bud development, duplication and aberrant positioning of the zone of polarizing activity in relation to the apical ectodermal ridge may account for the anatomic abnormalities of the hands and feet in these patients. © 1995 Wiley‐Liss, Inc.
Congenital ichthyosis preceding neurologic symptoms in two sibs with type 2 Gaucher disease
Authors: Fujimoto Atsuko , Tayebi Nahid , Sidransky Ellen
Published: June 2005

We describe 2 sibs who presented with ichthyotic skin at birth and subsequently developed neurologic manifestations of type 2 Gaucher disease. Type 2 Gaucher patients with and without ichthyosis manifest ultrastructural and biochemical abnormalities in the epidermis. The 2 patients described here clearly demonstrate that epidermal involvement in type 2 Gaucher disease may precede neurologic symptoms and substantiate the prognostic significance of early skin abnormalities in Gaucher patients. Gaucher disease should be considered in the differential diagnosis of congenital ichthyosis, even if the scaling resolves spontaneously. © 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.
Clinical findings in obligate carriers of type I Usher syndrome
Authors: Wagenaar M. , ter Rahe B. , van Aarem A. , Huygen P. , Admiraal R. , Bleeker‐Wagemakers E. , Pinckers A. , Kimberling W. , Cremers C.
Published: June 2005

Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal puretone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electrooculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities. © 1995 Wiley‐Liss, Inc.
Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome
Authors: Renieri Alessandra , Galli Lucia , Grillo Alessandra , Bruttini Mirella , Neri Tauro , Zanelli Paola , Rizzoni Gianfranco , Massella Laura , Sessa Adalberto , Meroni Mietta , Peratoner Leopoldo , Riegler Peter , Scolari Francesco , Mileti Maurizio , Giani Marisa , Cossu Maria , Savi Mario , Ballabio Andrea , De Marchi Mario
Published: June 2005

Mutations in the COL4A5 gene, which encodes the a5 chain of type IV collagen, are found in a large fraction of patients with X‐linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5′ ends of both COL4A5 and COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end‐stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome. © Wiley‐Liss, Inc.
Unique unbalanced X;X translocation (Xq22;p11.2) in a woman with primary amenorrhea but without Ullrich‐Turner syndrome
Authors: Letterie Gerard S.
Published: June 2005

This is a report of a patient with delayed puberty and a previously unreported translocation 46,X,−X,+der(X),t(X;X) (q22;p11.2) without any manifestations of Ullrich‐Turner syndrome. The relationship of this unbalanced translocation to the critical region hypothesis is discussed. © 1995 Wiley‐Liss, Inc.
Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder
Authors: Landau Daniel , Shalev Hana , Ohaly Meli , Carmi Rivka
Published: June 2005

The infantile variant of Bartter syndrome (IBS) is usually associated with maternal polyhydramnios, premature birth, postnatal polyuria and hypokalemic hypochloremic metabolic alkalosis and a typical appearance. IBS is thought to be an autosomal recessive trait. Several congenital tubular defects are associated with sensorineural deafness (SND). However, an association between the IBS and SND has not been reported so far. Here we describe 5 children of an extended consanguineous Bedouin family with IBS and SND. In 3 of the cases, the typical electrolyte imbalance and facial appearance were detected neonatally. SND was detected as early as age 1 month, suggesting either coincidental homozygotization of 2 recessive genes or a pleiotropic effect of one autosomal recessive gene. This association suggests that evaluation of SND is warranted in every case of IBS. © 1995 Wiley‐Liss, Inc.
Treatment of obstructive sleep apnea in achondroplasia: Evaluation of sleep, breathing, and somatosensory‐evoked potentials
Authors: Waters Karen A. , Everett Fay , Sillence David O. , Fagan Elizabeth R. , Sullivan Colin E.
Published: June 2005

The occurrence of obstructive sleep apnea (OSA) in achondroplasia has been linked to brain stem compression. Overnight sleep studies (11 subjects) and somatosensoryevoked potentials (SEP's, 10 subjects) were recorded before and after conventional treatment of OSA in achondroplasia. The two groups were derived from 30 subjects who underwent diagnostic sleep studies and SEPs, including 15 females and 15 males with a median age 6.6 of years (range 1.0–47.6) at the time of the first study. In 30 initial studies there was no correlation between severity of OSA and abnormalities on SEP evaluation. Treatment of 17 subjects included adenotonsillectomy (n = 3), weight loss (n = 1), and nasal‐mask continuous positive airway pressure (CPAP) (n = 13). Sleep studies in 11 subjects after a delay of 8.8 ± 2.8 months showed a reduction in respiratory disturbance index (RDI) from 38.4 ± 6.9 to 6.5 ± 1.8 events hr−1 (p < 0.001) and movements/arousals fell from 10.4 ± 2.2 to 4.8 ± 0.2 hr−1 (p < 0.04). Obstructive events were reduced from 33.7 ± 6.9 to 2.4 ± 1.0 hr−1 (p < 0.001). Improvement of respiratory indices was associated with an increased proportion of slow‐wave sleep from 25.2 ± 4.0% to 32.3 ± 2.4% (p = 0.01), and decrease in stage 1–2 sleep from 59.3 ± 5.8% to 46.6 ± 1.9% (p = 0.03). There was no increase in the percentage of REM sleep (15.2% to 21.2%). Repeat SEP studies in 10 subjects, after clinically effective treatment of OSA, showed improvement of SEP score of at least 1 grade, in 5 of 7 (71%) with initially abnormal values. We conclude that treatment to relieve upper airway obstruction improves OSA in achondroplasia, accompanied by changes in sleep structure and, in some cases, improved studies of neurological function. © 1995 Wiley‐Liss, Inc.
Hydrocephalus, skeletal anomalies, and mental disturbances in a mother and three daughters: A new syndrome
Authors: Ferlini Alessandra , Ragno Michele , Gobbi Paola , Marinucci Carlo , Rossi Roberto , Zanetti Adele , Milan Mario , Camera Gianni , Calzolari Elisa
Published: June 2005

We report on a family in which a mother and her 3 daughters have delayed psychomotor development and/or psychosis, hydrocephalus with white matter alterations, arachnoid cysts, skeletal anomalies consisting of brachydactyly, and Sprengel anomaly. Biochemical and cytogenetic analyses were normal on all 4 patients. The pattern of inheritance, clinical manifestations, and variability of expression suggest that this is a new hydrocephalus syndrome possibly transmitted as an X‐linked dominant trait. © 1995 Wiley‐Liss, Inc.
Lethal syndrome of slender bones, intrauterine fractures, characteristic facial appearance, and cataracts, resembling Hallermann‐Streiff syndrome in two sibs
Authors: Dennis Nicholas R. , Fairhurst Joanne , Moore Isabella E.
Published: June 2005

We report on a family in which 1 male infant who died neonatally and 1 female fetus at 29 weeks of gestation had an identical condition resembling Hallermann‐Streiff syndrome. The long bones were slender with a few fractures, the skull was underossified, and the face was characteristic of Hallermann‐Streiff syndrome. Bilateral cataracts were identified in the male. We regard the condition in this family as a severe form of Hallermann‐Streiff syndrome, which appears to have been lethal, at least in the liveborn male. This syndrome is usually sporadic. Recurrence in sibs suggests the possibility of autosomal‐recessive inheritance, or of a dominant mutation with parental mosaicism. © 1995 Wiley‐Liss, Inc.