bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and clinical heterogeneity of Stickler syndrome
Authors: Vintiner Gillian M. , Temple I. Karen , Middleton‐Price Helen R. , Baraitser Michael , Malcolm Sue 
Published: June 2005

AbstractWe have studied 6 multigeneration Stickler syndrome families. Manifestations of the syndrome in the families included myopia, deafness, arthritis, characteristic facial changes with “flat” midface and cleft palate, although not all these were present in all families. COL2A1 has been implicated as a gene which can give rise to Stickler syndrome based on evidence from 2 large families which each showed significant linkage between the disease locus and restriction fragment length polymorphisms for the gene (Francomano CA, Lieberfarb RM, Hirose T, Maumenee IH, Streeten EA, Meyers DA, Pyeritz RE (1987): Genomics 1:293–296; Knowlton RG, Weaver EJ, Struyk AF, Knobloch WH, King RA, Norris K, Shamban A, Uitoo J, Jimenez SA, Prockop DJ (1989): Am J Hum Genet 45:681–688). We have found crossovers between the disease locus and COL2A1 in 2 families with Stickler syndrome. This could be explained by either genetic heterogeneity or the actual mutation being in a closely linked, currently unrecognized gene. We found a weakly positive overall lod score (z = 0.96 at θ = 0.10) suggesting that genetic heterogeneity is a more likely explanation. In one family, with typical findings, a translocation t5;17 (q15:q23) was found to segregate with the disease in 4 affected relatives. In view of the possible heterogeneity, although no crossovers with COL2A1 were seen in this family, either of these breakpoints could be the position of a further disease causing gene.
Human chorionic gonadotrophin and trisomy 18
Authors: Barkai G. , Chaki R. , Sochat M. , Goldman B. 
Published: June 2005

AbstractEstimation of maternal serum β‐CG is used in conjunction with α‐fetoprotein (AFP) and estriol (E3) for estimating the risk of Down syndrome (DS) affected fetuses. However, low hCG levels have not been regarded as having clinical significance. We report on 2 patients with trisomy 18 fetuses in whom antenatal screening showed extremely low hCG levels (0.05 and 0.15 MOM). Low hCG levels might indicate increased risk for trisomy 18 despite low estimated risk for DS.
Hypomandibular faciocranial dysostosis: Report of an affected sib and follow‐up
Authors: Schimke R. Neil , Claflin Katherine S. , Seguin John H. , Bennett Timothy L. , Finley Brent E. , Levitch Lenna M. , Newcomb Ward M. 
Published: June 2005

AbstractHypomandibular faciocranial dysostosis is a condition heretofore described only in a single case. We report the birth of an affected sister along with follow‐up information on the initial surviving patient. While a primary error in neural crest development was postulated in this syndrome, subsequently discovered anatomical abnormalities suggest a more complex pathogenesis.
Research studies in applied human genetics: A quantitative analysis and critical review of recent literature
Authors: Lippman A. 
Published: June 2005

AbstractTo determine the extent to which speculations about the social, legal, and ethical implications of genetic counseling, screening, and prenatal diagnosis are being studied empirically, the substantive contents of major genetics (N=5) and obstetrics journals (N=2) from the years 1985–1989 were reviewed. Among the approximately 9,000 articles published, only 58 containing relevant substantive data could be identified. Data collected in a single study were reported in more than one article in at least ten cases so that these articles actually represent only 45 distinct studies. Most described investigations of the attitudes and reactions of individuals or couples who had had had or been referred for genetic counseling or prenatal diagnosis. These observational studies generally employe study‐specific questionnaires, many of which were apparently self‐administrered by respondents, to obtain data. This survey and analysis of the recent literature suggests that despite frequent editorials and othelr commentaries underlining the problematic nature of developments in medical genetics and calling for their investigation, the “gatekeepers” to this service continue to pay scant attention to these issues in their reported research. Innovative and interdisciplinary studies that will provide information to close the many gaps in ourunderstanding of the consequences of developments in applied human genetics are recommended for the furture.
Sacrococcygeal dysgenesis association
Authors: Duncan Peter A. , Shapiro Lawrence R. , Klein Robert M. 
Published: June 2005

AbstractIn the malformation analysis of 445 patients ascertained only for a sacrococcygeal malformation, a new phenotype, the sacrococcygeal dysgenesis association (SDA), was delineated in 34%. In addition, sirenomelia patients were found in 12%, the VATER association in 27%, and 27% could not be classified. Heterogeneity in the patients with sacrococcygeal malformations was identified by the differences found in their associated malformations.SDA patients have a relatively small average number (3.3) of anomalies per patient as compared with 9.3 in sirenomelia and 6.2 in VATER patients. SDA abnormalities occurred to a significant degree only in 6 of 20 designated malformation categories (vertebral, rib, pelvic, lower limb, central nervous system [CNS], renal) in contrast to 17 in VATER and 18 in sirenomelia patients. The SDA vertebral malformation pattern also differed from that of VATER/sirenomelia patients as did the high sacrococcygeal agenesis: dysgenesis ratio and low thoracolumbar vertebrae and/or rib hypersegmentations. Most significantly, SDA patients had a large number of CNS anomalies and CNS‐related dysfunctions of the urinary and distal intestinal tracts but no anatomic urinary or intestinal tract malformations. This contrasted sharply with the markedly increased occurrences of anatomic abnormalities in these body regions of the sirenomelia and VATER patients.Demographic data such as patient survival, twinning and, particularly, the high (28%) incidence of maternal diabetes in the SDA further support its differentiation from VATER/sirenomelia patients.
Diagnosis of tetrasomy 18p using in situ hybridization of a DNA probe to metaphase chromosomes
Authors: Park Vicki Murtif , Gustashaw Karen M. , Bilenker Robert M. , Golden Wendy L. 
Published: June 2005

AbstractWe identified an isochromosome of 18p [47, XY, + i(18p)] conclusively by in situ hybridization of an 18p‐specific probe (B74; D18S3) to metaphase chromosomes of an affected patient. Clinical findings included mental retardation, microcephaly, and an atrial septal defect. Although there is similarity to patients previously described with tetrasomy 18p, it is impossible to rule out a low frequency of mis‐diagnoses in karyotypes determined solely by standard cytogenetic analyses. We expect the ability to conclusively identify an i(18p) to lead to the delineation of tetrasomy 18p as a distinct clinical syndrome.
Weaver syndrome in two Japanese children
Authors: Kondo Ikuko , Mori Yuhko , Kuwajima Katsuko 
Published: June 2005

AbstractWe report on 2 Japanese patients (a 3‐year‐old girl and an 20‐month‐old boy) with the Weaver syndrome. The clinical manifestations are mild mental retardation, overgrowth with accelerated bone age, minor facial anomalies including broad forehead, mild hypertelorism, depressed nasal bridge, accentuated philtrum, micrognathia and large ears, and unique behavior characteristics with some social withdrawal. The nosology of the Weaver and Simpson–Golabi–Behmel syndromes is discussed.
Monozygotic twins of discordant sex both with 45, X/46, X, idic(Y) mosaicism
Authors: Fujimoto Atsuko , Boelter William D. , Sparkes Robert S. , Lin Ming S. , Battersby Kathleen 
Published: June 2005

AbstractA female twin with short stature, unusual facial appearance, widely spaced nipples, and coarctation of the aorta was found to have a peripheral blood lymphocyte karyotype of 45, X(43%)/46, X, idic(Y)(p11). Her twin brother, also short with similar facial appearance, had the same mosaicism (40% 45, X). Cultured skin fibroblast studies showed discrepant karyotypes of 45, X (100%) in the girl and 45, X (78%)/46, X, idic(Y)(p11) in the boy. The mother and the father had normal chromosomes. Comparison of 27 biochemical markers yielded a likelihood of monozygosity of 0.9977. This report documents the occurrence of discordant phenotypic sex in monozygotic twins, involving gonadal dysgenesis with an abnormal dicentric Y, which presumably occurred de novo, followed by anaphase lag probably before the occurrence of twinning. Unequal distribution of the two resultant cell lines in various tissues of each twin could account for the development of the very different phenotypes, apparently normal boy and Ullrich‐Turner girl.
Association of the Robin sequence with the fragile X syndrome
Authors: Lachiewicz Ave M. , Hoegerman Stanton F. , Holmgren Gösta , Holmberg Eva , Arinbjarnarson Kristian 
Published: June 2005

AbstractWe report on 4 individuals with the fragile X [fra(X)] syndrome and the Robin sequence (or elements of that sequence). To our knowledge, this association has been described in only one other boy. However, males with the fra(X) syndrome have been reported to have an increased incidence of cleft palate. We recommend that children with a cleft palate or the Robin sequence be assessed for developmental delays and a family history of mental retardation. The fra(X) syndrome may be one of the genetic causes of the Robin sequence and, when indicated, children with the sequence should be tested for fra(X).
Estimated number of loci for autosomal recessive severe nerve deafness within the Israeli Jewish population, with implications for genetic counseling
Authors: Brownstein Zipora , Friedlander Yechiel , Peritz Eric , Cohen Tirza 
Published: June 2005

AbstractDeafness occurs in about 1 per thousand live births, and at least 50% of congenital deafness is hereditary. The aim of this study was to examine the number of loci for recessively in herited severe nerve deafness of early onset within the Israeli population and to compare the results to those obtained in other populations. The Jewish population in Israel originates from many countries and may be divided into Sephardi, Eastern and Ashkenazi Jews, and the matings will be intraethnic or interethnic. Data were obtained on 133 deaf couples who lived in the Tel Aviv area, through the files of the Helen Keller Center. Causes of deafness in the spouses were studied and data on their children were obtained. Among 111 couples who had recessive or possibly recessive deafness and had at least 1 child, there were 12 with only deaf children and 5 with both deaf and hearing children. The number of loci for recessive deafness in the whole group was estimated at 8–9. Intraethnic and interethnic matings gave an estimate of 6.7 and 22.0 loci, respectively, which indicates that within populations fewer loci exist with recessive mutations for deafness than between populations. it could be shown that the sharing of loci between spouses decreased with increasing geographical distance of their origin. The results provide data for genetic counseling in Israel for deaf couples who have no children or have one hearing or one deaf child.
Mucolipidosis type IV: Clinical manifestations and natural history
Authors: Chitayat David , Meunier Catherine M. , Hodgkinson Kathy A. , Silver Kenneth , Flanders Michael , Anderson Ilse J. , Little John M. , Whiteman David A. H. , Carpenter Stirling 
Published: June 2005

AbstractThe clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi‐Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.
Familial congenital brachial palsy
Authors: Mollica F. , Volti S. Li , Grasso A. , De Simone D. 
Published: June 2005

AbstractEight relatives in a Sicilian family, including a sibship of 5, were affected with severe unilateral congenital brachial palsy (CBP) in a pattern suggesting autosomal dominant inheritance with reduced penetrance (6 cases affected on the right, 2 on the left). X‐linked inheritance with expression in heterozygous females cannot be excluded.
Early childhood diagnosis of acoustic neuromas in presymptomatic individuals at risk for neurofibromatosis 2
Authors: Pastores Gregory M. , Michels Virginia V. , Jack Clifford R. 
Published: June 2005

AbstractWe report on a family in which individuals at risk for NF 2 were investigated with the use of gadolinium‐enhanced MRI. This technique has allowed the diagnosis of small ( < 8 mm) acoustic neuromas in two asymptomatic children (age 7 and 11), one of whom had normal audiometric and brainstem‐evoked response testing. To our knowledge these are the youngest asymptomatic patients in whom the diagnosis of NF 2 has been demonstrated. It is possible that acoustic neuromas develop at an early age more commonly than recognized previously.The early diagnosis of acoustic neuromas with the use of gadolinium‐enhanced MRI may lead to better outcome following surgery. This technique will provide the opportunity to better determine the natural course of this disease.
Problems in ascertainment of transmitting males in Martin‐Bell syndrome
Authors: Loesch Danuta Z. , Hay David A. , Leversha Margaret 
Published: June 2005

AbstractThe difficulty of assigning families affected with the Martin‐Bell syndrome (MBS) into the category of male transmission is emphasised and illustrated by examples of 3 MBS families. These examples demonstrate how the ability to detect transmitting males depends on the number of generations available for investigation, and also on the “spread” of clinical investigation across many branches of the family regardless of what appears to be an unremarkable family history. Some unusual properties of male transmission are shown, and the problem of selective ascertainment of the particular MBS male individuals in different generations in a set of pedigrees is discussed.
Generalized chondrodysplasia punctata with shortness of humeri and brachymetacarpy: Humero‐metacarpal (HM) type: Variation or heterogeneity?
Authors: Borochowitz Zvi 
Published: June 2005

AbstractWe report on a girl with symmetrical rhizomelic shortness of the upper limbs and punctate epiphyseal calcifications noted at birth. Presumably she has normal height, but short nose, short hands, and normal mentation; and on roentgenograms short and wide humeri, symmetrical brachymetacarpy, especially of the 4th metacarpals, and hypoplastic distal phalanges, sagittal clefting of vertebral bodies, and punctate calcifications at various areas including the entire spine, sacrum, hands, feet, trachea, and thyroid cartilage. It is an apparently new syndrome of chondrodysplasia punctata (CP), quite distinct from the classic from (Conradi‐Hünerman type), as well as the other well‐defined forms of CP. We thus suggest the term chondrodysplasia punctata, humero‐metacarpal (HM) type.
De novo duplication of 17p [dup(17)(p12→p11.2)]: Report of an additional case with confirmation of the cytogenetic, phenotypic, and developmental aspects
Authors: Kozma Chahira , Meck Jeanne M. , Loomis Karen J. , Galindo Hugo C. 
Published: June 2005

AbstractWe describe an apparent de novo duplication of bands 17p11.2 and p12. A comparison of the manifestations of a previously reported case with a similar karyotype [Magenis et al., Am J Med Genet 24:415‐420 (1986)] and of our own case seems to indicate a characteristic pattern which includes prenatal and postnatal growth retardation, facial changes, club feet, and mild developmental deficits. The prominent facial changes are a relatively triangular face, downslanted palpebral fissures, malocclusion, and abnormal ears. In addition, this condition appears to be milder than other duplications of the short arm of chromosome 17, namely trisomy 17p and dup(17)(p11.2→cen).
Molecular analysis of gaucher disease: Screening of patients in the Montreal/Quebec region
Authors: Choy Francis Y. M. , Woo Mary , Der Kaloustian Vazken M. 
Published: June 2005

AbstractGaucher disease, the most prevalent lysosomal storage disease, is an autosomal recessive sphingolipidosis resulting from deficient glucocerebrosidase activity. Genomic DNA of the structural gene of glucocerebrosidase from normal individuals and fifteen unrelated patients with the three clinical forms of Gaucher disease from the Montreal/Quebec region were amplified by the polymerase chain reaction technique. Allele‐specific oli‐gonucleotide dot blot hybridization and restriction fragment length polymorphism were used to screen for five of the mutations [mutations 120, 370, 415, 444 (Nci), and 463] in exons 5,9, and 10 of glucocerebrosidase gene. It was noted that all of the patients had at least one of the known mutant alleles. However, 9 patients (9/15 = 60%) had an unknown allele. Mutation 370 in exon 9 was present in the heteroallelic form in eight out of the nine patients with type 1 Gaucher disease, but was present in none of the six patients with type 2 or type 3 Gaucher disease. The Nci mutation in exon 10 was present in the heteroallelic form in three patients with type 1 Gaucher disease and in either the heteroallelic or homoallelic form in all of the six patients with type 2 or type 3 Gaucher disease. The 415/Nci mutations were found in a mildly affected 29‐year‐old patient with type 1 Gaucher disease, as well as in an infant with the type 2 form. These findings demonstrate the clinical and molecular genetic heterogeneities of Gaucher disease, the presence of unknown Gaucher allele(s) in most (60%) of the patients surveyed, and the occasional inexplicable lack of phenotype‐genotype correlation among some patients. It also suggests that other genetic factor(s) may be implicated in determining the phenotypic expression of Gaucher disease.
Campomelia, polycystic dysplasia, and cervical lymphocele in two sibs
Authors: Urioste Miguel , Arroyo Antonio , Martínez‐Frías María‐Luisa 
Published: June 2005

AbstractWe report on 2 sibs with a similar MCA pattern consisting of generalized lymphedema, cervical lymphocele, shortness of limbs, bowed long bones, and multicystic kidneys with fibrotic liver or pancreas. To our knowledge, this is the second observation of such a combination of defects in sibs, and it confirms the existence of the syndrome reported by Cumming et al. [1986] and its autosomal recessive inheritance.
Hallermann‐Streiff syndrome with hypopituitarism contributing to growth failure
Authors: Pivnick Enikö K. , Burstein Stephen , Sid Wilroy R. , Kaufman Robert A. , Ward Jewell C. 
Published: June 2005

AbstractA 35‐month‐old black boy with Hallermann–Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be some what altered due to his racial background. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.
Respiratory obstruction and cor pulmonale in the Hallermann‐Streiff syndrome
Authors: Robinow Meinhard 
Published: June 2005

AbstractThe risk of respiratory death in the Hallermann‐Streiff syndrome is not insignificant, particularly in the neonatal period and in infancy. Upper airway obstruction may result from small nares and glossoptosis secondary to micrognathia, which sometimes lead to cor pulmonale. I report on a patient with such problems.
Genetic analysis of cleft lip with or without cleft palate in Madras, India
Authors: Nemana Lakshmi J. , Marazita Mary L. , Melnick Michael 
Published: June 2005

AbstractWe performed a genetic analysis of 331 nonsyndromic cleft lip with or without cleft palate (CL ± P) proband families ascertained in Madras, India. Predictions of the multifactorial threshold (MF/T) model are tested; goodness‐of‐fit tests of the MF/T model and complex segregation analysis are also utilized to clarify the genetic etiology of CL ± P in this study population. There was little evidence for the MF/T model. The most reasonable conclusion from mixed model analysis is that of a major locus with reduced transmission probability. This is not altogether surprising if manifestation of CL ± P also depends on in utero exposure to harmful environmental agents during the critical period of facial development, as suggested by Melnick et al. [1980] and demonstrated in an animal model of CL ± P [Melnick et al., 1981]. Further the results in the Madras population are quite similar to those in other populations of Europe and Asia.
Ectopia lentis and aortic root dilatation in congenital contractural arachnodactyly
Authors: Bawle Erawati , Quigg Mary Helen 
Published: June 2005

AbstractCongenital contractural arachnodactyly (CCA) was described by Beals and Hecht as an autosomal dominant disorder distinct from Marfan syndrome and comprising joint contractures, arachnodactyly, scoliosis, and a distinct “crumpled ear” deformity. While the disorder is similar to Marfan syndrome, it was split from it due to the distinct physical appearance of the patients and, more importantly, the lack of heart and eye findings. Since the original report, several CCA patients have been found to have mitral valve prolapse, structural cardiac anomalies, and occasionally aortic root dilatations similar to those seen in Marfan syndrome. We report on a patient with CCA with bilateral ectopia lentis and aortic root dilatation. Our review of the literature of CCA showed that serial echo‐cardiography and careful eye examinations have not become a standard of medical practice in this condition. Partly this may be due to a lack of documented cases of CCA having severe ectopia lentis and cardiac complications. This patient underscores the need for periodic eye and echocardiographic evaluations of all CCA patients.