bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal diagnosis of partial trisomy 1q using fluorescent in situ hybridization
Authors: DuPont B. R. , Huff R. W. , Ridgway L. E. , Stratton R. F. , Moore C. M.
Published: June 2005

We report the use of fluorescent in situ hybridization (FISH) with a DNA library of chromosome 1‐specific probes to confirm the karyotype, 46,XY,15, + der15,t(1;15)(q32.1; q26.3), obtained by prenatal periumbilical blood sampling from a fetus who exhibited multiple abnormalities by ultrasound examination. GTG‐banding of chromosomes obtained from the mother showed a normal karyotype, while the father was unavailable for study. The propositus was born at 37 weeks gestation and survived for several weeks. Cytogenetic analysis performed after the birth of the male infant with multiple anomalies verified partial trisomy 1q. This patient is compared with other partial trisomy 1q patients reported in the literature. The usefulness of FISH is demonstrated in situations where fetal abnormalities are present with de novo chromosomal rearrangements where paternal chromosomes are unavailable for study. © 1994 Wiley‐Liss, Inc.
Fallot complex, severe mental, and growth retardation: A new autosomal recessive syndrome?
Authors: Bindewald Bettina , Ulmer Herbert , Müller Ulrich
Published: June 2005

We report on the syndromic occurrence of the Fallot complex in sibs born to consanguineous Pakistani parents. Additional manifestations included minor facial anomalies, pronounced failure to thrive, and mental retardation. Expression of the syndrome varied. While one of the four patients had cardiac malformations, another sib had only non‐cardiac manifestations. The clinical findings suggest a new autosomal recessive syndrome. © 1994 Wiley‐Liss, Inc.
Sexing of human embryos and fetuses by fluorescent in situ hybridization (FISH) to paraffin‐embedded tissues with sex chromosome‐specific DNA probes
Authors: Mori Chisato , Shiota Kohei
Published: June 2005

A fluorescent in situ hybridization (FISH) study was carried out on paraffin sections of human embryonic and fetal tissues with two DNA probes, DXZ1 and DYZ1 (Oncor), for X and Y chromosome‐specific DNA sequences, respectively. The specificity of the DNA probes was confirmed on metaphase and interphase lymphocytes of healthy normal adult males. The paraffin blocks of the human embryonic and fetal tissues examined in the present study had been stored at room temperature for up to 5 years after fixation in 4% paraformaldehyde. All the seven embryos and five fetuses examined were successfully sexed by FISH. The cells from three embryos and four fetuses were positive for a hybridization signal with each of the DXZ1 and DYZ1 probes and they were classified as male. The cells from the remaining four embryos and one fetus were positive for two identical hybridization signals with the DXZ1 probe in a nucleus instead of the absence of the signal hybridized with DYZ1, indicating that their cells have two X chromosomes but no Y chromosomes. The FISH results for the five fetuses examined were consistent with their genital sex and/or gonadal histology. The FISH results were highly specific and no false positive or false negative results were obtained. Thus, the FISH technique has been shown to visualize specific DNAs in situ on paraffin sections and to be useful to determine the sex of fixed embryos and fetuses retrospectively. © 1994 Wiley‐Liss, Inc.
Familial crossed polysyndactyly
Authors: Goldstein David J. , Kambouris Marios , Ward Richard E.
Published: June 2005

We have observed a distinct form of “crossed” polysyndactyly in 6 generations of a family with 5 affected persons, all males. The polydactyly is postaxial in the hands and preaxial in the feet. Syndactyly in the hands is observed in some relatives, while syndactyly in the feet is present bilaterally in all affected relatives. This seems to be an autosomal dominant trait with male to male transmission over 3 generations by examination and an additional 3 generations by history.

This form of polysyndactyly could not be readily categorized by the existing classification by Temtamy and McKusick [1978: BD OAS XIV 6:363–392]. We review and expand the present classification of polydactyly and syndactyly syndromes. © 1994 Wiley‐Liss, Inc.
Psychological aspects of genetic counseling: A legal perspective
Authors: Sharpe Neil F.
Published: June 2005

Carrier and presymptomatic genetic testing information can have profound psychological consequences for a patient and the family. American and Canadian professional accreditation standards for clinical genetics state that the health care provider must be prepared to provide psychological support. Through a survey of human/medical genetics journals and texts, this article identifies those protocols that constitute an appropriate standard of care, and examines the legal implications, particularly with regard to the law of medical malpractice. © 1994 Wiley‐Liss, Inc.
Novel karyotype in the Ullrich‐Turner syndrome—45,X/46,X,r(X)/46,X,dic(X)—investigated with fluorescence in situ hybridization
Authors: Robson L. , Jackson J. , Cowell C. , Sillence D. , Smith A.
Published: June 2005

A 10‐year‐old girl with Ullrich‐Turner syndrome was found to have the novel karyotype 45,X/46,X,r(X)(p11q11)/46,X,dic(X)(p11). Fluorescence in situ hybridization (FISH) with the α satellite X centromere probe established the origin of the small ring chromosome. Scanning a large number of cells by interphase FISH showed that the dicentric (X) was the least prevalent cell line. The common breakpoint of Xp11 suggests a sequence of errors as the mechanism whereby these 3 distinct cell lines have arisen. © 1994 Wiley‐Liss, Inc.
Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G)
Authors: Pastores Gregory M. , Santorelli Filippo M. , Shanske Sara , Gelb Bruce D. , Fyfe Billie , Wolfe David , Willner Judith P.
Published: June 2005

Mutation of mitochondria) (mt) DNA at nucleotide (nt) 8993 has been reported to cause neurogenic weakness, ataxia, retinitis pigmentosa (NARP), or Leigh syndrome (LS). We report a family in whom the mutation was expressed clinically as LS and hypertrophic cardiomyopathy (CMP) in a boy who presented with a history of developmental delay and hypotonia, and who had recurrent lactic acidosis. The mother's first pregnancy resulted in the birth of a stillborn female; an apparently healthy older brother had died suddenly (SIDS) at age 2 months. MtDNA analysis identified the presence of the T8993G point mutation, which was found to be heteroplasmic in the patient's skeletal muscle (90%) and fibroblasts (90%). The identical mutation was present in leukocytes (38%) isolated from the mother, but not from the father or maternal grandmother. Our findings expand the clinical phenotype of the nt 8993 mtDNA mutation to include hypertrophic cardiomyopathy and confirm its cause of LS. © 1994 Wiley‐Liss, Inc.
Clinical findings in two African‐American families with the nevoid basal cell carcinoma syndrome (NBCC)
Authors: Goldstein Alisa M. , Pastakia Berham , Digiovanna John J. , Poliak Susanna , Santucci Sandra , Kase Ronald , Bale Allen E. , Bale Sherri J.
Published: June 2005

The nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder with variable expressivity. We present the clinical findings on 11 African‐American NBCC cases from 2 families and a review of the literature of NBCC in African‐Americans. The 2 new families, as well as those previously reported, suggest minimal expression of the basal cell carcinomas and full expression of the other components of the syndrome. The 3 most common findings in the 11 cases were jaw cysts, palmar and/or plantar pits, and calcification of the falx cerebri. Only 44% (4/11) of these cases had one or more confirmed basal cell carcinomas. This frequency is substantially less than that observed in whites (90% with basal cell carcinomas). The relative lack of these skin tumors in African‐Americans partly reflects ultraviolet radiation protection resulting from increased skin pigmentation. Future research should help identify the specific mutation(s) in blacks as well as other modifying genes and environmental exposures that may contribute to the varied manifestations of the syndrome. © 1994 Wiley‐Liss, Inc.
Nevoid basal cell carcinoma syndrome: Review of 118 affected individuals
Authors: Shanley Susan , Ratcliffe John , Hockey Athel , Haan Eric , Oley Christine , Ravine David , Martin Nicole , Wicking Carol , Chenevix‐Trench Georgia
Published: June 2005

One hundred eighteen cases of nevoid basal cell carcinoma syndrome (NBCCS, Gorlin's syndrome or basal cell nevus syndrome) are presented in this study. In aiming to ascertain all the affected families in Australia, we have examined the largest series to date. Relative frequencies of associated complications are presented and compared with those of the recent English survey by Evans et al. [J Med Genet 30:460–464, 1993]. The frequencies of most manifestations are similar. However, one major difference is that the multiple basal cell carcinomas are manifest from an earlier age in the Australian population, which probably reflects greater exposure to ultraviolet radiation. Of the 64 families ascertained, 37 represented simplex cases, and, accordingly, the apparent new mutation rate is surprisingly high (14–81%) given the lack of impact of NBCCS on reproductive capabilities. There is some evidence to suggest that this may be attributable to anticipation. © 1994 Wiley‐Liss, Inc.
Coincident DiGeorge anomaly and renal agenesis and its relation to maternal diabetes
Authors: Novak Robert W. , Robinson Haynes B.
Published: June 2005

We describe 2 cases of DiGeorge anomaly with bilateral renal agenesis–one, who also had hemivertebrae, in an infant of an insulin–dependent diabetic mother (IDDM). In a review we identified 2 other instances of this combination, both in IDDMs. The currently accepted notion that DiGeorge anomaly and renal agenesis are developmental field defects, coupled with their coincidence in IDDM, suggests that this combination is an association. © 1994 Wiley‐Liss, Inc.
Cholesterol metabolism in the RSH/Smith‐Lemli‐Opitz syndrome: Summary of an NICHD conference
Authors: Opitz John M. , de la Cruz Felix
Published: June 2005

During the evolution of multicellularity and attendant processes of development, cholesterol played a key role in the formation of the plasma membrane and outer mitochondrial membrane of every cell in the organism. Later functions include pivotal involvement in steroid, bile acid, and vitamin D metabolism and myelination of the nervous system. In the CNS myelination does not begin until the third trimester, and subcortical myelination not until after birth. The cholesterol of the cell membrane of the ovum is maternally derived. It is not known when the zygote begins making its own cholesterol during morphogenesis and histogenesis, but it must occur early to keep up with the dramatic rate of cell division in the embryo. Thus, it is a startling surprise that human embryos and fetuses apparently able to synthesize little cholesterol (because of a presumed defect of the Δ5,7‐sterol, Δ7‐reductase that converts 7‐dehydrocholesterol (7‐DHC) into cholesterol) frequently live to term and, rarely, may be so mildly affected as to attend school with only mild MR. The discovery by G. Stephen Tint and his co‐workers of the apparent 7‐DHC reductase deficiency makes the RSH (Smith‐Lemli‐Opitz) syndrome the first true metabolic malformation syndrome. A teratological animal model which has been known for 30 years now appears applicable to the RSH/SLO syndrome. A multidisciplinary NICHD conference held on September 20–21, 1993 reviewed the numerous implications of this discovery and agreed unanimously that research in this field be given highest priority in order to better understand cholesterol synthesis in the mammalian brain, cholesterol transport from mother to embryo and fetus, pre‐and postnatal metabolic compensation in structure and function for a profound block in cholesterol synthesis, the nature of the blood–brain barrier for cholesterol, treatment of affected infants, children, and adults, structure and genetic specification of a 7‐DHC reductase enzyme (which has never been purified!) and its evolution, the variability of the syndrome and whether it is genetically homo‐ or heterogeneous, the population genetics of the RSH syndrome, possible selective advantages (or disadvantages) of heterozygotes, and means of newborn screening, carrier detection, and prenatal diagnosis. © 1994 Wiley‐Liss, Inc.
Abnormal cholesterol metabolism in the Smith‐Lemli‐Opitz syndrome: Report of clinical and biochemical findings in four patients and treatment in one patient
Authors: Irons Mira , Elias Ellen Roy , Tint G. S. , Salen Gerald , Frieden Roger , Buie Timothy M. , Ampola Mary
Published: June 2005

We report on four patients with the Smith‐Lemli‐Opitz (SLO) syndrome who appear to have a defect in cholesterol biosynthesis. The initial results of therapy of one of the patients with cholesterol and bile acids to correct her metabolic abnormalities are described. This finding provides a biochemical marker to help in the diagnosis of this syndrome, may provide insight into the pathogenesis of this disorder, and have therapeutic and prenatal diagnostic implications as well. © 1994 Wiley‐Liss, Inc.
Smith‐Lemli‐Opitz syndrome in a female with a de novo, balanced translocation involving 7q32: Probable Disruption of an SLOS gene
Authors: Wallace Margaret , Zori Roberto T. , Alley Tiffany , Whidden Elaine , Gray Brian A. , Williams Charles A.
Published: June 2005

A 3‐month‐old infant girl had manifestations of the Smith‐Lemli‐Opitz syndrome (SLOS) including typical positional anomalies of the limbs, apparent Hirschsprung disease, cataracts, ptosis, anteverted nares, cleft of the posterior palate, small tongue, broad maxillary alveolar ridges, and abnormally low serum cholesterol levels. Chromosomal analysis showed a de novo balanced translocation interpreted as 46,XX,t(7;20)(q32.1;q13.2). We hypothesize that the translocation breakpoint in this case interrupts one SLOS allele and that the other allele at the same locus has a more subtle mutation that was inherited from the other parent. This case, as well as cytogenetic observations in other SLOS cases, suggests that SLOS could be due to autosomal recessive mutation at a gene in 7q32. © 1994 Wiley‐Liss, Inc.
Mosaic tetrasomy 8p in two patients: Clinical data and review of the literature
Authors: Schrander‐Stumpel Constance T. R. M. , Govaerts Lutgarde C. P. , Engelen John J. M. , van der Blij‐Philipsen Marianne , Borghgraef Martine , Loots Wil J. G. , Peters Jan J. M. , Rijnvos Wilhelmina P. M. , Smeets Dominique F. C. M. , Fryns Jean‐Pierre
Published: June 2005

We report on 2 girls with mosaic tetrasomy 8p. Patient 1 showed the extra iso 8p chromosome in 20% of cultured lymphocytes and 18% of cultured fibroblasts [46,XX/47,XX, + i(8p)]. She presented with growth retardation, mild facial alterations, and motor developmental delay. Patient 2 presented with developmental delay, hypotonia, and slight facial alterations; she had the extra iso 8p chromosome in 94% of cultured peripheral lymphocytes. The patients are compared to the 6 previously reported cases. In our experience, the presently reported patients clinically resemble children with inv dup(8)(p21‐p22) and patients with mosaic trisomy 8. © 1994 Wiley‐Liss, Inc.
Gene for Simpson‐Golabi‐Behmel syndrome is linked to HPRT in Xq26 in two European families
Authors: Orth Ulrike , Gurrieri Fiorella , Behmel Annemarie , Genuardi Maurizio , Cremer Marion , Gal Andreas , Neri Giovanni
Published: June 2005

Linkage, analysis was performed in 2 previously described European families segregating for the Simpson‐Golabi‐Behmel (SGB) syndrome. In both kindreds close linkage without recombination (zmax=4.45 at theta= 0.00) was observed between the disease locus and the HPRT locus mapped in Xq26. These data are very similar to those (zmax=7.5 at the‐ta=0.00) reported recently by others after studying a large Dutch‐Canadian kindred with SGB syndrome. Compiled lod scores from the 3 families reach their maximum of 11.95 at recombination fraction of 0.00 with one lod unit support interval of 0.00–0.04. © 1994 Wiley‐Liss, Inc.
Multiple congenital anomalies in a man with (X;6) translocation
Authors: Sivak Louise E. , Esbenshade John , Brothman Arthur R. , Issa Bonnie , Lemons Richard S. , Carey John C.
Published: June 2005

X;autosome translocations in humans, often associated with congenital anomalies or with gonadal dysgenesis syndromes, are informative for the study of X‐linked gene expression and of the phenomenon of X chromosome inactivation. When such translocations occur in association with multiple congenital anomaly (MCA) syndromes, the observed phenotypes are not always attributable solely to disruption of specific genes, if X‐inactivation spreads onto the translocated autosome, rendering some distal genes inactive. We report on a man with multiple congenital anomalies and a maternally inherited (X;6)(p22.1;p25) translocation. He has abnormalities not described in the Klinefelter or 6p deletion syndromes. His unique findings constitute a recognizable syndrome, which is likely caused by disomy for a region of Xp in conjunction with a partial 6p deletion. © 1994 Wiley‐Liss, Inc.
Regional proteus syndrome and somatic mosaicism
Authors: Smeets Eric , Fryns Jean‐Pierre , Cohen M. Michael
Published: June 2005

We report on a patient with regional manifestations of Proteus syndrome. Major findings included multiple hyperostoses of the calvaria, facial bones, and mandible. Additionally, the patient had a scleral tumor. This lends further support to the hypothesis of somatic mosaicism as a cause of Proteus syndrome. Because mosaic distribution of lesions is variable in extent, criteria for the diagnosis of Proteus syndrome should be loose rather than overly rigid even though patients with limited regional involvement may be particularly difficult to diagnose. © 1994 Wiley‐Liss, Inc.
Neurological involvement in worth type endosteal hyperostosis: Report of a family
Authors: Adès L. C. , Morris L. L. , Burns R. , Haan E. A.
Published: June 2005

We present the first Australian family known with autosomal dominant endosteal hyperostosis affecting a mother and her 2 children. Neurological involvement comprising chronic intracranial hypertension and cranial nerve palsies were found in the mother; computerised tomography and magnetic resonance imaging of the head demonstrated symmetrical sclerosis of the cranial vault, narrow internal auditory meati and canals, inferior herniation of the cerebellar tonsils into the foramen magnum, and encroachment of occipital bone into the foramen magnum posteriorly. This is the fifth report of significant neurologic involvement in this condition and supports the view that severe forms of endosteal hyperostosis are not confined to the autosomal recessive variant, as individuals with the autosomal dominant form may also show progression with neurological involvement in adulthood. © 1994 Wiley‐Liss, Inc.
Acrocallosal syndrome in two African brothers born to consanguineous parents
Authors: Christianson Arnold L. , Venter Philip A. , Du Toit Joan L. , Shipalana Nancy , Gericke George S.
Published: June 2005

We describe two mentally retarded brothers with craniofacial anomalies, polydactyly, and other clinical manifestations compatible with the acrocallosal syndrome (ACS). These are the first black patients from Africa with this diagnosis. They are also the fourth set of sibs described with ACS, and together with the parental consanguinity documented in this family, confirm autosomal recessive inheritance of this syndrome. The clinical manifestations in our patients confirm the intrafamilial variability of the syndrome. Postnatal onset of growth retardation is proposed as an additional manifestation of ACS. © 1994 Wiley‐Liss, Inc.
Mitochondrial myopathy with anemia, cardiomyopathy, and lactic acidosis: A distinct late onset mitochondrial disorder
Authors: Van Hove Johan L. K. , Shanske Sara , Ciacci Federica , Ballinger Scott , Shoffner John S. , Wallace Douglas C. , Hanioka Takashi , Folkers Karl , Bossen Edward H. , Kussin Peter S. , Kopita Jeffrey M. , Kahler Stephen G.
Published: June 2005

A 40‐year‐old woman presented with pro found muscle weakness resulting in failure to wean from a ventilator and persistent lactic acidosis after having recovered from a pneumonia complicated by adult respiratory distress syndrome, myocardial infarction, renal failure and shock. She had a 28 year history of chronic anemia and exercise intolerance. Anemia and thrombocytopenia persisted after admission. Nonobstructive hypertrophic cardiomyopathy was present. A stroke‐like episode occurred. A mitochondrial myopathy with deficiencies in complexes IV and II was demonstrated, but no DNA defect has yet been found. This patient represents a distinct clinical presentation of a mitochondrial disorder characterized by late onset mitochondrial myopathy, chronic anemia, cardiomyopathy, and lactic acidosis. © 1994 Wiley‐Liss, Inc.
Infant with multiple congenital anomalies and deletion (9)(q34.3)
Authors: Schimmenti Lisa A. , Berry Susan A. , Tuchman Mendel , Hirsch Betsy
Published: June 2005

We report on a male infant with developmental delay, growth failure, hypotonia, dolichocephaly, hypoplastic midface, epicanthal folds, down‐slanting palpebral fissures, foveal hypoplasia, tracheomalacia, pectus excavatum, supraventricular tachycardia, gut malrotation, hypospadias, talipes equinovarus, short third metatarsals, capillary hemangiomata, and a de novo terminal deletion at 9q34.3. © 1994 Wiley‐Liss, Inc.
Localization of branchio‐oto‐renal (BOR) syndrome to a 3 Mb region of chromosome 8q
Authors: Wang Y. , Treat K. , Schroer R. J. , O'Brien J. E. , Stevenson R. E. , Schwartz C. E.
Published: June 2005

Branchio‐oto‐renal (BOR) syndrome is an autosomal dominant condition of branchial arch anomalies, deafness and renal dysplasia. Clinical manifestations tend to have considerable intrafamilial and interfamilial variability. Previous linkage studies had localized the gene responsible for BOR syndrome to a broad region of chromosome 8q. Using 10 microsatellite markers, we have further refined the localization of this disorder by establishing tight linkage to two markers, D8S279 and D8S530 (Zmax = 3.91 and Zmax = 2.83 respectively at Θ = 0.00. These markers are within 1 cM of one another. Multipoint analysis, involving 7 loci, placed the gene between these markers, with a lod‐1 confidence interval 0.7 cM proximal to D8S530 and 0.6 cM distal to D8S279. © 1994 Wiley‐Liss, Inc.
Refined localization of the branchiootorenal syndrome gene by linkage and haplotype analysis
Authors: Ni Li , Wagner Michael J. , Kimberling William J. , Pembrey Marcus E. , Grundfast Kenneth M. , Kumar Shrawan , Daiger Stephen P. , Wells Dan E. , Johnson Kristin , Smith Richard J. H.
Published: June 2005

Branchiootorenal (BOR) syndrome is a common autosomal dominant form of hearing impairment previously mapped to 8q. This report refines the localization of the BOR syndrome gene by haplotype analysis to the interval flanked by markers D8S553 and D8S286. By multipoint linkage analysis, the disease locus most likely is flanked by markers D8S530 and D8S279. © 1994 Wiley‐Liss, Inc.
GAPO syndrome in a child without dermal hyaline deposit
Authors: Phadke Shubha R. , Haldhar Ashutosh , Sharma Anita K. , Pande Rakesh , Bhatia Vijayalakshmi , Agarwal S. S.
Published: June 2005

A 5‐year‐old girl with GAPO syndrome from India lacked PAS‐positive hyaline material in the skin biopsy from thigh and scalp. The role of this pathological change, earlier reported by Wajntal et al. [1990] in the pathogenesis of GAPO syndrome, needs to be reexamined. © 1994 Wiley‐Liss, Inc.
Microcephalic osteodysplastic dysplasia
Authors: Hersh J. H. , Joyce M. R. , Spranger J. , Goatley E. C. , Lachman R. S. , Bhatt S. , Rimoin D. L.
Published: June 2005

We Present two patients with a distinct facial phenotype, short stature, brachydactyly, clubfoot deformities, cataracts, microcephaly, and normal intelligence. Similar radiographic abnormalities of the spine, long bones, hands, and feet were noted. These patients are similar to 2 males previously described by Saul and Wilson [1990: Am J Med Genet 35:388–393]. These 4 patients appear to have a unique skeletal dysplasia characterized by microcephaly, distinct facial phenotype, multisystem abnormalities, and short stature of postnatal onset. © 1994 Wiley‐Liss, Inc.
Cerebrovascular stenoses with cerebral infarction in a child with Williams syndrome
Authors: Ardinger Robert H. , Goertz Kenneth K. , Mattioli Leone F.
Published: June 2005

We report on a patient with Williams syndrome who suffered a cerebrovascular accident. Clinical evaluation demonstrated the presence of carotid and cerebral arterial stenoses. We believe these lesions led to acute cerebrovascular ischemia and a non‐hemorrhagic cerebral infarction. It is possible the stenoses were exacerbated by a vasculitis. The stenoses were identified by both invasive and noninvasive imaging studies. These studies may have a role in the evaluation of persons with Williams syndrome. © 1994 Wiley‐Liss, Inc.
Severe spondylocostal dysostosis associated with other congenital anomalies: A clinical/epidemiologic analysis and description of ten cases from the Spanish registry
Authors: Martínez‐Frías María‐Luisa , Bermejo Eva , Paisàn Luis , Martín Martín , Egüés Javier , López José‐Antonio , Martínez Salvador , Orbea Carlos , Cucalón Fermín , Gairi Josep‐María , Urioste Miguel , de la Cruz María‐Angeles
Published: June 2005

We describe 10 cases born to nondiabetic mothers who presented with severe spondylocostal dysostosis (SCD) associated with other anomalies, identified among 20,526 malformed liveborn infants from the Spanish Collaborative Study of Congenital Malformations (ECEMC). We analyze the associated malformations in the 10 cases with severe SCD, as well as in all cases with less severe SCD among children with MCA patterns of unknown cause.

Cases with SCD were preferentially associated with caudal dysgenesis, diaphragmatic hernia, and central nervous system anomalies. © 1994 Wiley‐Liss, Inc.
Blepharophimosis, telecanthus, microstomia, and unusual ear anomaly (Simosa syndrome) in an infant
Authors: Suri Mohnish , Kabra Madhulika , Verma Ishwar C.
Published: June 2005

We report on a 1‐month‐old infant with blepharophimosis, telecanthus, ear anomalies, and microstomia. He also had a long philtrum and a narrow, high‐arched palate. This case is very similar to the cases re‐ported by Simosa et al. [1989: Am J Med Genet 32:18–186]. In addition, our patient had tongue tie and camptodactyly of fingers. © 1994 Wiley‐Liss, Inc.
Increased risk for type I (insulin‐dependent) diabetes in relatives of patients with alopecia areata (AA)
Authors: Wang Sue‐Jane , Shohat Tamar , Vadheim Constance , Shellow William , Edwards Joel , Rotter Jerome I.
Published: June 2005

The prevalence of various chronic diseases was compared in 517 individuals with alopecia areata, and 2,969 of their first degree relatives. As previous reports have suggested an increased incidence of diabetes in relatives of patients with alopecia areata, special attention was given to the prevalence of Type 1 and Type 2 diabetes in the patients and in their relatives. Several immunologic diseases were increased in alopecia probands and relatives. Thyroid disease, vitiligo, Addison disease, and pernicious anemia were more prevalent in probands and in their relatives than in the general population. Specifically, a high rate of thyroid disease was found in probands (14.7%) and in their first degree relatives (4.2%). Only one proband had Type 1 diabetes, yet there were 14 sibs with Type 1 diabetes. Thus, Type 1 diabetes was significantly more prevalent in the sibs (1.2%) than in either the probands with alopecia (0.2%), or the general population (0.12–0.25%) (P < 0.05)). In contrast, Type 2 diabetes was not more common in probands or in sibs than in the general population. These data suggest that alopecia areata protects against Type 1 diabetes in predisposed individuals. The high rate of thyroid disease suggests that screening probands and first degree relatives for thyroid disease should be considered. © 1994 Wiley‐Liss, Inc.
Split hand/split foot, syndactyly, urinary tract obstruction, radial, diaphragmatic, and neural tube defects: Czeizel‐Losonci syndrome?
Authors: Genuardi Maurizio , Silvestri Evelina , Tozzi Carla
Published: June 2005

We report on a baby girl with absence of the left hemidiaphragm, lumbosacral myelomeningocele, syndactyly with limb deficiencies, and bilateral hydronephrosis. A similar array of malformations was described previously by Czeizel and Losonci [Hum Genet 77:203–204, 1987] in a single family which showed a transmission pattern suggesting autosomal dominant inheritance with variable expressivity. The presence of limb abnormalities and the location of the neural tube defects in these cases suggest that the underlying pathogenesis probably does not involve the same disturbances of midline field development which have been postulated to occur in the schisis association. © 1994 Wiley‐Liss, Inc.
Blepharophimosis, ptosis, epicanthus inversus syndrome, a new case associated with de novo balanced autosomal translocation [46,XY,t(3;7)(q23;q32)]
Authors: Boccone Loredana , Meloni Antonella , Falchi Angela M. , Usai Valeria , Cao Antonio
Published: June 2005

This paper reports a further case of blepharophimosis, ptosis, epicanthus inversus (BPES) syndrome associated with a reciprocal translocation [46,XY,t(3;7)(q23;q32)], involving band 3q23. This case supports the assignment of a BPES gene(s) to the 3q23 region. © 1994 Wiley‐Liss, Inc.
High functioning fragile X males: Demonstration of an unmethylated fully expanded FMR‐1 mutation associated with protein expression
Authors: Hagerman Randi J. , Hull Claire E. , Safanda John F. , Carpenter Isabelle , Staley Louise W. , O'Connor Rebecca A. , Seydel Charlotte , Mazzocco Michele M. M. , Snow Karen , Thibodeau Stephen N. , Kuhl Derek , Nelson David L. , Caskey C. Thomas , Taylor Annette K.
Published: June 2005

Fragile X (fra(X)) males with a standardized IQ score of 70 or higher represent a high functioning (HF) or nonretarded fra(X) male group. This group, which does not include nonpenetrant males, has received little research attention to date. Of 221 fra(X) males who had been evaluated through The Children's Hospital in Denver since 1981 and had completed cognitive or developmental testing, 29 (13%) were high functioning by the above definition. We found that HF males on the whole had a lower cytogenetic score and were younger than retarded fra(X) males, but there was no difference between these two groups in the number of typical fra(X) physical manifestations present. FMR‐1 DNA testing was performed on 134 fra(X) males and methylation status was determined for 51 of these. A greater percentage of HF males had a mosaic pattern or an incompletely methylated full mutation than did retarded males. A unique DNA pattern, an unmethylated fully expanded mutation, was discovered in 3 of the highest functioning fra(X) males. Protein studies performed on 2 of these males demonstrated the presence of FMR‐1 protein, albeit at lower levels than normal. FMR‐1 protein was not present in retarded fra(X) males. Significant FMR‐1 protein expression may be responsible for higher cognitive functioning in the 2 males with unmethylated fully expanded mutations compared to retarded fra(X) males. © 1994 Wiley‐Liss, Inc.
No apparent involvement of the FMR1 gene in five patients with phenotypic manifestations of the fragile X syndrome
Authors: Chiurazzi Pietro , de Graaff Esther , Ng Jessica , Verkerk Annemieke J. M. H. , Wolfson Sloan , Fisch Gene S. , Kozak Libor , Neri Giovanni , Oostra Ben A.
Published: June 2005

Most fragile X patients have a significant increase in the number of CGG repeats in the FMR1 gene. Two patients were described with a deletion and one patient with a point mutation in the FMR1 gene. We describe 5 patients with a fragile X or Martin‐Bell phenotype. Two brothers were discordant for the region containing the FMR1 gene; if there is a common cause for the mental retardation this is not located in the FMR1 gene. In the other 3 patients the expression of the FMR1 gene was found to be normal and no abnormalities were noted in the FMR1 mRNA. No amplification was found in the GCC repeat which is associated with the fragile site FRAXE. We conclude that the Martin‐Bell phenotype can also be caused by mutations outside the FMRl gene. © 1994 Wiley‐Liss, Inc.
Modeling methylation and IQ scores in fragile X females and mosaic males
Authors: Kolehmainen Karen , Karant Yasha
Published: June 2005

Both fragile X females and mosaic males carry a methylated FMR1 allele in some cells and an unmethylated allele in other cells. Due to FMR1 protein produced in cells with an unmethylated allele, these individuals are expected to display a less severe cognitive phenotype than non‐mosaic affected males. A larger range in cognitive abilities is expected for these individuals due to individual variation in X‐inactivation or mosaicism ratios. These cognitive effects are well documented for females and have been suggested for mosaic males. Data on fragile X females suggest an approximately linear decrease in mean IQ score as a function of the fraction of cells with the mutation carried on the active X chromosome. Analysis of these data suggests that threshold effects in the relationship between IQ score and X‐inactivation ratios are negligible, and that X‐inactivation occurs randomly (with no preferential inactivation of either X chromosome) at a stage when the embryo consists of approximately 5 cells. A similar analysis of future data on mosaic males could yield estimates of the probability that a given cell will carry a methylated FMR1 allele and of the number of embryonic cells at the time that mosaicism is established. Distributions of IQ scores among a population of heterozygotes or mosaic males are predicted for several values of these parameters. These distributions include random contributions to IQ scores due to non‐fragile‐X‐related effects, as well as X‐inactivation or mosaicism ratios that vary from one individual to another. © 1994 Wiley‐Liss, Inc.
Emotional and neurocognitive deficits in fragile X
Authors: Sobesky William E. , Pennington Bruce F. , Porter Deborah , Hull Claire E. , Hagerman Randi J.
Published: June 2005

We have studied the neurocognitive deficit in premutation and full mutation women as compared to control women and to explore the relationship between those deficits and the incidence of emotional problems. Four groups of women were examined: two fragile X (fra(X)) negative control groups, one of which grew up in fra(X) families and one not; and two DNA positive groups, one with a premutation (CGG repeats <200) and one with an expanded mutation (CGG repeats >200). All women were assessed using the MMPI‐2, the SADS‐L, and a battery of neuropsychological tests.

Full mutation women had lower scores on composite measures of executive function and nonverbal function. There was no difference between the groups in terms of the lifetime incidence of depressive and anxiety disorders on the SADS‐L. Full mutation women displayed Lie scales higher than the other groups on the MMPI‐2. Neurocognitive measures were not related to SADS‐L diagnoses but were related to the Lie scale on the MMPI‐2. Finally, number of CGG repeats was related to the neuropsychological variables and the Lie scale.
Distribution of FMR‐1 and associated microsatellite alleles in a normal Chinese population
Authors: Zhong Nan , Liu Xixian , Gou Shen , Houck George E. , Li Shuyun , Dobkin Carl , Brown W. Ted
Published: June 2005

The CGG repeat size distribution of the fragile X mental retardation gene (FMR‐1) was studied in a population of normal Chinese X chromosomes along with that of two proximal microsatellite polymorphic markers: FRAXAC1 and DXS548. The most common CGG repeat allele was 29 (47.2%) with 30 being second most common (26%). This distribution was different from that seen in Caucasian controls, where the most common allele was 30 repeats. Other differences with Caucasian controls included a secondary modal peak at 36 repeats and the absence of peaks at 20 or 23 repeats. There were only two FRAXAC1 and five DXS548 alleles found in the Chinese sample. A striking linkage disequilibrium of FMR‐1 alleles with FRAXAC1 alleles was observed, in that 90% of the 29 CGG repeat alleles but only 41% of the 30 CGG repeat alleles had the FRAXAC1 152 bp allele (18 AC repeats). This disequilibrium suggests that slippage between the closely spaced normal CGG repeat alleles, 29 and 30, and between 152 and 154 FRAXAC1 alleles is very rare. This study lays the groundwork for an understanding of founder chromosome effects in comparing Asian and Caucasian populations. © 1994 Wiley‐Liss, Inc.
DNA diagnosis of the fragile X syndrome in a series of 236 mentally retarded subjects and evidence for a reversal of mutation in the FMR‐1 gene
Authors: van den Ouweland Ans M. W. , de Vries Bert B. A. , Bakker P. Lida G. , Deelen Wout H. , de Graaff Esther , van Hemel Jan O. , Oostra Ben A. , Niermeijer Martinus F. , Halley Dicky J. J.
Published: June 2005

The cloning of the FMR‐1 gene and the identification of an expanded CGG repeat in DNA of fragile X patients has made reliable DNA diagnosis feasible. Southern blotting and PCR assays of the CGG repeat in an unselected series of 236 mentally retarded subjects resulted in the identification of 10 new fragile X families. Reevaluation of previously assessed fragile X families resulted in the first observation of the presence of a reversal of mutation in the FMR‐1 gene. © 1994 Wiley‐Liss, Inc.
Non‐specific X‐linked mental retardation: Linkage analysis in MRX2 and MRX4 families revisited
Authors: Hu Ling‐Jia , Blumenfeld‐Heyberger Sandra , Hanauer André , Weissenbach Jean , Mandel Jean‐Louis
Published: June 2005

We have previously reported linkage analysis in 3 families with non‐specific X‐linked mental retardation (XLMR). This used RFLPs and was limited by the relatively low informativeness and density of markers available. We have performed a new linkage analysis using microsatellites (including new Genethon markers) in the two most informative families. In the MRX2 family, a lod score of 2.61 at θ = 0.05 had previously been obtained with DXS85 in Xp22.2. We now report a tighter linkage with AFM 135xe7 (DXS989, z = 4.62 at θ = 0.00) and established the order DXS85‐DXS207‐DXS999 (AFM234yf12)‐MRX2, DXS365, DXS1052 (AFM 163yh2), DXS989‐DXS1065 (AFM224zf2), DMD 3′. The localization of MRX2 in Xp22.2‐p22.1 is thus clearly different from the more distal MRX gene defined by patients with contiguous gene syndromes. In the MRX4 family, a maximum lod score of 2.53 at θ = 0.00 had been obtained with DXS159 in Xq13. Our present study did not show recombination from ALAS2 in Xp11.21 to DXS441 in Xq13.3 (z = 3.38 at θ = 0.00 for the latter marker) and the closest flanking markers are DXS255 in Xp11.22 and DXYS1 in Xq21.3. Reduced recombination around the centromere prevents precise mapping. The localisation of MRX4 overlaps with that of several other MRX families. © 1994 Wiley‐Liss, Inc.
X‐linked mental retardation with heterozygous expression and macrocephaly: Pericentromeric gene localization
Authors: Turner G. , Gedeon A. , Mulley J.
Published: June 2005

A family is described with X‐linked mental retardation (XLMR) with affected males in 2 generations. The manifestations are macrocephaly and heterozygous expression. Linkage analysis gives a 2‐point lod score of 3.31 (θ = 0.0) at the AR, DXS991, and MAOB marker loci. The gene is localized by recombination events between DXS1068 (Xp) and DXS1125 (Xq). This condition in this family may be similar to that described by Atkin et al., 1985 (Am J Med Genet 21:697–705).
X‐linked mental retardation, microcephaly, and growth delay associated with hereditary bullous dystrophy macular type: Report of a second family
Authors: Lungarotti M. Serena , Martello Cecilia , Barboni Giancarlo , Mezzetti Daniele , Mariotti Giacomo , Calabro Anna
Published: June 2005

We report on 2 patients with mental retardation and bullous dystrophy, macular type. The observation of the condition in a male and his maternal uncle is consistent with recessive X‐linkage. Due to the rarity of the condition, nosologic definition was difficult before the birth of the propositus. The clinical picture in the two patients described, characterized by mental retardation, dwarfism, microcephaly, alopecia, bullous dystrophy macular type, hypogenitalism, is very much like the one observed in the patients, all males, belonging to the only other family reported to date. The recent localization of the bullous dystrophy gene in the Xq24‐qter segment opens the possibility of prenatal diagnosis. © 1994 Wiley‐Liss, Inc.
Marked female predilection in some syndromes associated with facial hemangiomas
Authors: Gorlin Robert J. , Kantaputra Piranit , Aughton David J. , Mulliken John B.
Published: June 2005

Analysis of the literature yielded 42 examples of the combination of sternal non‐union and supraumbilical raphé without evidence of sex predilection. However, among an additional 31 cases in which the triad included facial hemangioma, there was almost exclusive female occurrence.

Another condition involves extensive unilateral hemangioma of the face, absence of ipsilateral carotid and vertebral vessels, mental retardation, and Dandy‐Walker malformation. Still another disorder has been proposed which includes facial hemangioma and dilatation of the carotid syphon. Both of these conditions exhibit marked female predilection.

Examples of overlap of all three “disorders” cause the authors to question the independence of these disorders, hypothesizing instead that they represent a spectrum. © 1994 Wiley‐Liss, Inc.
Diamniotic placentation associated with omphalopagus conjoined twins: Implications for a contemporary model of conjoined twinning
Authors: Kapur Raj P. , Jack Rhona M. , Siebert Joseph R.
Published: June 2005

We have studied omphalopagus conjoined twins with a diamniotic monochorionic placenta. Although conjoined twins usually present in a single amniotic sac, one other example of diamniotic placenta has been reported in omphalopagus twins [Weston et al., 1990: Am J Med Genet 37:558–561]. Most theories concerning the pathogenesis of conjoined twinning exclude the possibility of diamniotic placentation. However, Spencer [1992: Teratology 45:591–602] recently elaborated a model for conjoined twinning based on duplication of organizing centers (primitive streaks) during gastrulation. We have considered the fate of embryonic membranes according to this model of omphalopagus twinning and show that diamniotic placentation is a predictable outcome. © 1994 Wiley‐Liss, Inc.
DK‐phocomelia syndrome in a child with a long follow‐up
Authors: Urioste Miguel , Paisán Luis , Martínez‐Frías María Luisa
Published: June 2005

We report on an 8‐year‐old boy with a pattern of multiple congenital anomalies that strongly suggest DK‐phocomelia syndrome. Birth findings included bilateral upper limb amelia, occipital encephalocele, agenesis of the corpus callosum, right auricular tag, scoliosis, small penis, and cryptorchidism. Dental malocclusion was observed in the follow‐up. This is the first case with on 8‐year follow‐up report of DK‐phocomelia syndrome. © 1994 Wiley‐Liss, Inc.
Six additional cases of the KBG syndrome: Clinical reports and outline of the diagnostic criteria
Authors: Zollino M. , Battaglia A. , D'Avanzo M. G. , Bruna M. M. Della , Marini R. , Scarano G. , Cappa M. , Neri G.
Published: June 2005

A diagnosis of KBG syndrome was made in six unrelated patients. They presented with slight mental retardation, macrodontia, and skeletal abnormalities. Microcephaly, short stature, facial anomalies, and syndactylies were also noted. The diagnostic criteria of the KBG syndrome are discussed. © 1994 Wiley‐Liss, Inc.
Familial Dandy‐Walker malformation associated with macrocephaly, facial anomalies, developmental delay, and brain stem dysgenesis: Prenatal diagnosis and postnatal outcome in brothers. A new syndrome?
Authors: Chitayat David , Moore Lori , Del Bigio Marc R. , MacGregor Daune , Ben‐Zeev Bruria , Hodgkinson Kathy , Deck John , Stothers Tammy , Ritchie Susan , Toi Ants
Published: June 2005

Brothers are reported with an apparently new constellation of manifestations including Dandy‐Walker complex (DWC), migrational brain disorder, macrocephaly, and facial anomalies. The first brother presented at birth, the second was detected prenatally with DWC and the pregnancy terminated. Fetal brain histopathology showed DWC associated with brainstem dysgenesis. Inheritance is likely autosomal or X‐linked recessive. An extensive review of the differential diagnosis of DWC is provided. © 1994 Wiley‐Liss, Inc.
Fetal t(5p;21q) misdiagnosed as monosomy 21: A plea for in situ hybridization studies
Authors: Gill Prabhcharan , Uhrich Stefanie , Disteche Christine , Cheng Edith
Published: June 2005

We report a case of 45,XY,−5,−21,+der (5) t(5;21) (p13 or p14;q11.2 or q21) that was prenatally misdiagnosed as complete monosomy 21 and terminated at 24 weeks of gestation. Subsequent fluorescence in situ hybridization studies with a chromosome 21 painting probe documented the cryptic unbalanced translocation. © 1994 Wiley‐Liss, Inc.
New autosomal dominant form of spondyloepiphyseal dysplasia presenting with atlanto‐axial instability
Authors: Reardon W. , Hall C. M. , Shaw D. G. , Kendall B. , Hayward R. , Winter R. M.
Published: June 2005

We present a family with a radiologically distinct new form of autosomal dominant spondyloepiphyseal dysplasia, presenting with cervical instability and attendant neurological compromise and emphasise the radiological characteristics which delineate this condition. Cervical vertebral abnormalities, including malformation of the odontoid process, have been observed in some forms of spondyloepiphyseal dysplasia, but rarely lead to neurological sequelae, in contrast to the pedigree we describe. © 1994 Wiley‐Liss, Inc.
Velo‐cardio‐facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region
Authors: Nickel Robert E. , Pillers De‐Ann M. , Merkens Mark , Magenis R. Ellen , Driscoll Deborah A. , Emanuel Beverly S. , Zonana Jonathan
Published: June 2005

Approximately 5% of children with neural tube defects (NTDs) have a congenital heart defect and/or cleft lip and palate. The cause of isolated meningomyelocele, congenital heart defects, or cleft lip and palate has been largely thought to be multifactorial. However, chromosomal, teratogenic, and single gene causes of combinations of NTDs with congenital heart defects and/or cleft lip and palate have been reported. We report on 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of velo‐cardio‐facial syndrome (VCFS); both also have bifid uvula. The third child had DiGeorge sequence (DGS).

The association of NTDs with 22q11 deletions has not been reported previously. An accurate diagnosis of the 22q11 deletions is critical as this micro‐deletion and its associated clinical problems is transmitted as an autosomal dominant trait due to the inheritance of the deletion‐bearing chromosome. We recommend that all children with NTDs and congenital heart defects, with or without cleft palate, have cytogenetic and molecular studies performed to detect 22q11 deletions. © 1994 Wiley‐Liss, Inc.