摘要:

AbstractAs part of an epidemiological study of congenital hydrocephalus in Utah, we focused on the effect of ascertainment sources and temporal variability to further delineate the causes of this relatively common, handicapping birth defect. The incidence and distribution of 934 reported cases diagnosed prior to age 6 months, and born to Utah residents from 1940 to 1979, were analyzed. Data were ascertained by examination of multiple sources, e.g., 982,066 birth, 11,161 fetal death, and 248,208 death certificates, and selected hospital and clinic records. Of the 934 reported cases, 700 met our selection criteria for congenital hydrocephalus, which results in a crude incidence of 0.70 per 1,000 live and stillbirths. Seventy‐one cases (10.1%) had additional, multiple congenital anomalies. The male/female sex ratios of the 619 cases of isolated congenital hydrocephalus (occurring as a single entity or in the absence of other reported or known birth defects) and those with multiple congenital anomalies (71 cases) were virtually identical, being 1.45 and 1.48, respectively. A significant 85% increase in the rate of reported cases was observed for the period 1966 to 1970. However, examination of patients' records from 1966 to 1975 in the hospital responsible for almost all of this increase suggests that this was an iatrogenically related “epidemic” caused by several factors: the introduction and possible misinterpretation of pneumoencephalograms (PEG) in the diagnosis of hydrocephalus (PEG was replaced by CAT scanning in the early 1970s), inappropriate diagnosis, and incorrect recording of age at time of diagnosis. © 1994 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractAnalysis 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

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractFour cases having mosaicism for a small marker or ring [45,X/46,X,+mar or 45,X/46,X,+r] chromosome were ascertained following cytogenetic studies requested because of minor anomalies (cases 1, 3, and 4 ) and/or short stature (cases 2 and 4). While all 4 cases had traits typical of Ullrich‐Turner syndrome (UTS), cases 1, 3, and 4 had manifestations not usually present in UTS, including unusual facial appearance, mental retardation/developmental delay (MR/DD) (cases 3 and 4), and syndactylies (case 1). The facial appearances of cases 1 and 3 were similar yet distinct from that of case 4.Using fluorescence in situ hybridization (FISH), each of the markers in these 4 cases was identified as having been derived from an X chromosome. The level of mosaicism for the mar/r(X) cell line in these cases varied from 70% (case 1) to 16% (case 4) but was not apparently correlated with the presence of MR/DD. Replication studies demonstrated a probable early replication pattern for the mar/r(X) in cases 1,3, and 4, while the marker in case 2 was apparently late replicating.To date, 41 individuals having mosaicism for a small mar/r(X) chromosome have been described. Interestingly, most of the 14 individuals having a presumedly active mar/r(X) demonstrated clinical findings atypical of UTS, including abnormal facial changes (11) and MR/DD (13). MR was noted most frequently in those cases having at least 50% mosaicism for the marker or ring. In contrast, atypical UTS facial appearance or MR/DD was not noted in 14 of the 16 cases with UTS who carried a probable late replicating marker or ring.In conclusion, although the phenotype of 45,X/46,X,mar/r(X) individuals appears to be influenced by the genetic content and degree of mosaicism for the mar/r(X), the most significant factor associated with MR/DD appears to be the activity status of the mar/r(X) chromosome. Thus, our 4 cases provide further support for the hypothesis that a lack of inactivation of a small mar/r(X) chromosome may be a factor leading to the MR and other phenotypic abnormalities seen in this subset of individuals having atypical UTS. © 1994 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe allele for pseudodeficiency (PD) of the lysosomal enzyme arylsulfatase A (ARSA) is a common polymorphism in all populations. The PD allele frequency in different Israeli ethnic groups was found to range from 9.2–22.7%. The PD allele includes two different mutations PD (1) and PD (2) in an aproximatively 1 Kb interval. In this study we confirmed that while PD (1) may be found alone as a polymorphism, PD (2) is always associated with the PD allele (660 alleles screened). Analysis of three ARSA intragenic polymorphisms showed a complete linkage disequilibrium between the PD allele and an haplotype defined by the three polymorphic restriction sites. The results suggest that the origin of the PD polymorphism may be a common founder, or recurrent mutations which are occurring in a unique haplotype. © 1994 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractPreimplantation genetics describes a newly‐emerging field in medical genetics, the consequence of the implementation of clinical preimplantation diagnosis and the likely future development of germ‐line gene therapy. Given the existing clinical and laboratory difficulties already demonstrated in preimplantation diagnosis and the sensitive ethical issues surrounding genetic manipulation of human embryos, there is a need for 1) critical and objective evaluation of developments in this field by human and medical geneticists and 2) development of guidelines for research and clinical practice in the years ahead. We propose a course of prospective action for preimplantation genetics implemented through the newly‐formed American College of Medical Genetics in order to address the ethics, safety, accuracy, cost, and overall merit of preimplantation genetics. © 1994 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular techniques. On the basis of molecular findings, the patients were classified into the following 4 groups: familial cases without deletion, familial cases with submicroscopic deletion, sporadic cases with deletion, and sporadic cases without deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion which commonly extended fromD15S9toD15S12, although not all deletions were identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion involving only 2 loci,D15S10andGABRB3, which define the critical region for AS phenotypes. The parental origin of deletion, both in sporadic and familial cases, was exclusively maternal and consistent with a genomic imprinting hypothesis. Among sporadic and familial cases without deletion, no uniparental disomy was found and most of them were shown to inherit chromosomes 15 from both parents (biparental inheritance). A discrepancy between cytogenetic and molecular deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis could be performed. Ten (43%) of 23 patients with a normal karyotype showed a molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15) (q11q13), showed no molecular deletion. Most clinical manifestations, including neurological signs and facial characteristics, were not distinct in each group except for hypopigmentation of skin or hair. Familial cases with submicroscopic deletion were not associated with hypopigmentation. These findings suggested that a gene for hypopigmentation is located is located outside the critical region of AS and is not imprinted. © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe Bardet‐Biedl syndrome is an autosomal recessive disorder of polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and renal involvement. A high incidence of congenital and acquired heart disease was reported in the former “Laurence‐Moon‐Biedl‐Bardet” syndrome. However, since the establishment of the Bardet‐Biedl syndrome as a separate clinical entity, cardiac involvement has not been evaluated in this disorder. We have performed echocardiographic studies on 22 patients with the Bardet‐Biedl syndrome from three extended, highly inbred Bedouin families. In addition to previously reported congenital heart defects we have observed hypertrophy of the interventricular septum and dilated cardiomyopathy. Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow‐up of patients with Bardet‐Biedl syndrome. ©

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractKnobloch syndrome is a rare genetic disorder characterized by high myopia, vitreoretinal degeneration with retinal detachment and occipital cephalocele. The inheritance has been described as autosomal recessive (AR) but in addition to the original report with 5 affected patients [Knobloch and Layer, 1971] only one other family with 2 affected sibs has been described [Czeizel et al., 1992]. We have studied a large consanguineous kindred in which there are 12 patients with severe ocular alterations associated with a congenital occipital encephalocele, compatible with the diagnosis of Knobloch syndrome. CT scan and MRI performed in one of the patients, allowed a better understanding of the cranial and ocular alterations in this syndrome. The pattern of occurrence in this highly inbred family clearly confirms autosomal recessive inheritance of Knobloch syndrome. © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe Treacher Collins‐Franceschetti syndrome (TCOF) or mandibulofacial dysostosis (MFD) is an autosomal dominant disorder characterized by craniofacial abnormalities and hearing loss. A refined genetic linkage map of the TCOF locus was established in 8 independent families, using 12 microsatellite DNA markers of the distal 5q. Positive lod score values were obtained for all markers with a maximum at the D5S413 locus (Zmax = 3.79 at θ = 0%). Multipoint linkage analysis and haplotype analysis supported the location of the gene between loci D5S434 and D5S412. These results are consistent with previous linkage analysis [Dixon et al.: Am J Hum Genet 49:17–22, 1991, Am J Hum Genet 52:907–914, 1993; Jabs et al.: Genomics 11:193–198, 1991, Genomics 18:7–13, 1993] and provide further evidence of genetic homogeneity in this syndrome. © 1994 Wile

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe report on an infant who presented at birth with some characteristics of trisomy 18 syndrome, including low birth weight, facial abnormalities, overlapping fingers, and congenital heart defects. On chromosome analysis, no additional chromosome 18 was observed and both chromosome 18 homologues appeared normal. However, a small piece of chromosomal material of unknown origin was detected at the tip of the long arm of chromosome 1. Fluorescence in situ hybridization (FISH) using whole chromosome 18 painting probes disclosed no additional hybridization at the telomere of 1q, suggesting that the material was derived from another chromosome. Further chromosome painting experiments suggested that the telomeric addition was of chromosome 1 origin. To identify subchromosomal regions involved in the rearrangement, additional FISH analyses were performed using single copy and repetitive DNA probes mapping to different portions of chromosome 1. The analyses showed that probes mapping to 1q34‐43 were duplicated in the derivative chromosome 1. In addition, a DNA probe mapping to 1q44 was found to be deleted from the derivative chromosome 1. Our composite analysis suggests that a deletion and a duplication of chromosome 1q can result in some of the clinical findings usually associated with trisomy 18 syndrome. These results demonstrate the usefulness of FISH analysis when karyotype analysis is not consistent with the clinical description. © 1994 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320520211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY