ISSN:0148-7299    

DOI:10.1002/ajmg.1320420202

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

年代:1992

数据来源: WILEY

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420203

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe present a balanced translocation (X;9) (q28;q21) in which the normal X chromosome is preferentially active. The derivative X chromosome is inactive in 93% of fibroblasts, but the X portion translocated onto chromosome 9 is not inactivated, as apparent from DNA methylation and chromosome replication patterns. Consequently, the patient is functionally disomic for the part of Xq28 distal to the locus LICAM.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420204

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe reviewed 122 cases of balanced X‐autosome translocations in females, with respect to the X inactivation pattern, the position of the X break point and the resulting phenotype.In 77% of the patients the translocated X chromosome was early replicating in all cells analysed. The break points in these cases were distributed all along the X chromosome. Most of these patients were either phenotypically normal or had gonadal dysgenesis, some had single gene disorders, and less than 9% had multiple congenital anomalies and/or mental retardation.In the remaining 23% of the cases the translocated X chromosome was late replicating in a proportion of cells. In these cells only one of the translocation products was reported to replicate late, while the remaining portion of the X chromosome showed the same replication pattern as the homologous part of the active, structurally normal X chromosome. The analysis of DNA methylation in one of these cases confirmed noninactivation of the translocated segment. Consequently, these cells were functionally disomic for a part of the X chromosome. The presence of disomic cells was highly prevalent in translocations with break points at Xp22 and Xq28, even though spreading of X inactivation onto the adjacent autosomal segment was noted in most of these cases. This suggests that selection against cells with a late replicating translocated X is driven predominantly by a functional disomy X, and that the efficiency of this process depends primarily on the position of the X break point, and hence the size of the noninactivated region. Since the persistence of cells with a late replicating translocated X was usually associated with mental retardation and other abnormalities, it is concluded that the outcome of the selection process against the functional disomy X is the major determinant of the clinical status in most patients with balanced X‐autosome translocati

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420205

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

年代:1992

数据来源: WILEY

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420206

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

年代:1992

数据来源: WILEY

摘要:

AbstractDetailed physical mapping of oto‐palato‐digital (OPD) syndrome gene on the X‐chromosome was attempted on a family of 3 generations with 2 affected men. Although the result remains statistically non‐significant, it indicates that the OPD‐I gene might be located on the

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420207

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

年代:1992

数据来源: WILEY

摘要:

AbstractLeber hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by bilateral acute or subacute loss of central vision, primarily in young males. A G→A single base mutation at 11778nt of the mitochondrial genome which eliminates a SfaNI restriction site [Wallace et al., 1988; Holt et al., 1989; Hotta et al., 1989; Singh et al., 1989; Vilkki et al., 1989; Yoneda et al., 1989; Stone et al., 1990; Lott et al., 1990.] has been found in more than 60% of the families with LHON studied.We studied 25 persons from 4 families with LHON using SfaNI and Mae III digestion of a 201 base pair polymerase chain reaction (PCR) product encompassing the 11778nt mutation. The loss of the SfaNI site and the acquisition of a Mae III site at 11778nt were identified in all maternal relatives of the LHON families studied. The mutation was heteroplasmic in all affected individuals, female carriers, and males at‐risk. The heteroplasmy of mitochondrial DNA (mtDNA) was also identified by direct DNA sequencing of PCR amplified mtDNA digested by SfaNI or Mae III. It appears that the proportion of the mutant mtDNA correlates with the severity of the dise

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420208

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe report on a stillborn boy with frontonasal malformation (Sedano‐J̌iràsek type D—DeMyer type I), associated with encephalocoele, occipital meningocele and preaxial polydactyly of the feet. This form of frontonasal dysplasia was documented previously in a few other cases with various combinations of postaxial polydactyly, tibial hypoplasia, epibulbar dermoid, occipital encephalocoele, corpus callosum agenesis and Dandy‐Walker malformation. Most cases are s

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420209

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

年代:1992

数据来源: WILEY

摘要:

AbstractVarious theories have been postulated to account for the unusual inheritance pattern observed in the fragile X syndrome. The recent finding of a secondary amplification of the fragile X mutation in the offspring of carrier females [Oberle et al., 1991; Yu et al., 1991] is consistent with a maternal imprinting process. Laird [1987]has proposed that the fragile X mutation blocks complete reactivation of a previously inactivated fragile X chromosome. We have tested whether or not such a localized block extends as far distal as the red/green color‐vision complex at Xq28. We found no evidence of color‐vision defects among 25 male subjects with the fragile X syndrome. A fragile X positive woman also had normal color vision, despite being an obligate carrier of her father's gene for red/green color blindness. We conclude that the fragile X gene does not affect the function of neighboring colorvision genes, nor does it affect their ability to compensate adequately for inherited color deficiency on the homologous X chromosome in fema

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420210

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

年代:1992

数据来源: WILEY

摘要:

AbstractA survey ofMendelian Inheritance in Manemphasizes the large Mendelian contribution to human dysmorphogenesis and contrasts single gene conditions with chromosomal disorders. There were 1761 conditions that involved altered morphogenesis (49% of disease entries), including 1040 multiple defect syndromes and 721 inherited single birth defects. Premature death (36–57%), mental retardation (20–59%), and growth retardation (37–59%) are more frequent in autosomal recessive or X‐linked syndromes, while predisposition to tumorigenesis was more common in dominant (16%) than recessive (3.4%) syndromes. Comparison of the Mendelian conditions with 100 chromosomal disorders showed a strikingly similar spectrum of malformation, with skeletal, craniofacial, eye, epidermal, and neuromuscular systems being most frequently affected. Chromosomal syndromes average 10.6 systems affected per disorder, in contrast to 3.55 for Mendelian syndromes, and pleiotropy does correlate weakly with aneuploid segment length. Genomic understanding of these relationships is still primitive, with 74 of 1609 (4.6%) autosomal conditions and 43 of 152 (29%) X‐linked conditions mapped to specific chromosomal regions. The societal toll of human dysmorphogenesis and the evident progress with X‐linked disorders provide a powerful rationale for the Human Gen

ISSN:0148-7299    

DOI:10.1002/ajmg.1320420211

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

年代:1992

数据来源: WILEY