摘要:

AbstractA large Sardinianfamily including 13 Martin‐Bell syndrome (MBS) patients, several instances of normal transmitting males or females, and the G6PD‐Mediterranean mutant segregating in some of its branches, has been thoroughly investigated with the hope of gaining further insight on the nature of the FRAX‐mutation. All the MBS patients and the 15 obligate heterozygous women present in the pedigree could be traced back through their X‐chromosome lineage to the same ancestress, who must have been heterozygous for a silent premutation at the FRAX‐locus. This premutation appears to have turned into a true FRAX‐mutation at least 9 times during the gametogenesis of the ancestress' X‐related descendants of whom four are males. This finding alone suggests that the transition from the FRAX premutation to the true mutation can be the result of intra‐ as well as interchromosomal events. This conclusion is supported by the additional observation that the genetic phase between the FRAX and the G6PD loci remained unaltered when the transition occurred in a repulsion double heterozygote for the premutation and the G6PD‐Mediterranean mutant. The data described are compatible with the hypothesis that MBS patients and normal transmitting males are, respectively, hemizygous for deletion or duplication products generated by aberrant recombination events at a highly recombinogenic site of the region Xq27‐Xqter. The overall message stemming from this report is that no firm conclusion can be drawn on the genetic linkage between the FRAX‐locus and other markers of this region until the nature of the FRAX‐mutations and the mechanism of their occurren

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400402

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

年代:1991

数据来源: WILEY

摘要:

AbstractHall‐Pallister syndrome is defined by specific facial anomalies, post axial polydactyly, imperforate anus, and brain anomalies including a rare diencephalic mass, hypothalamic hamartoblastoma. In this article, two patients are described with the usual features of Hall‐Pallister syndrome, including diencephalic anomalies, but without hamartoblastomas. These patients may suggest an appropriate extension of the definition of the Hall‐Pallister syn

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400403

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

年代:1991

数据来源: WILEY

摘要:

AbstractBy means of an appropriate mathematical model (Sager's 2‐components‐concept) a delayed spontaneous pubertal growth spurt can be demonstrated in girls with 45, X Ullrich‐Turner syndrome (UTS) (n1= 45) as well as in those with 45, X/46,XX mosaicism (n2= 14) never treated with any growth stimulating drug. On the average, this growth spurt begins later and its extent is smaller (mean growth rate = 3.10 and 2.79 cm, respectively, in the 15th year of chronological age) than in normal girls. The delay in acute growth spurt corresponds very well to the delay of skeletal maturation in the UTS (on the average 2 to 3 years of chronological

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400404

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe describe 14 males from 3 successive generations in a family who have X‐linked mental retardation (XLMR), obesity, gynecomastia, speech difficulties, emotional lability, tapering fingers, and small feet. Linkage analysis using markers spread along the X chromosome demonstrated a gene localisation close to the centromere. Maximum lod scores for markers near the centromere, all at θ= 0.00, were 1.36 forDXS7, 4.82 forDXS255, 2.79 forDXS14, 2.09 forDXS72, and 1.46 forDXYS1. The closest flanking markers which showed recombination wereDXS84, andDXS94, defining the physical localisation within Xp21.1‐q22.DXS255was fully informative with lod‐1 confidence interval for θ of 0.00–0.12. Clinical findings and linkage data in this family distinguish it from the Börjeson‐Forssman‐Lehmann syndrome and other previously described

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400405

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe report a possible new syndrome in a female abortus with the following abnormalities: ectrodactyly limited to the feet, a “simplified” ear pattern, mild retrognathism, highly arched palate, spina bifida of open myelomeningocele type, membranous type ventricular septal defect, and single umbilical art

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400406

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe report on an autosomal dominant syndrome comprising partially absent eye muscles, anterior chamber defects, hydrocephalus, skeletal changes, and a specific facial phenotype.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400407

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

年代:1991

数据来源: WILEY

摘要:

AbstractAlström disease is a rare disorder; less than 20 cases have been reported. An 11‐year‐old girl is described with this condition. She has pigmentary retinopathy, sensory neural deafness, obesity, Type II diabetes mellitus, hyperlipidemia, and acanthosis nigricans. However, in addition she developed hepatic dysfunction, pathologically similar to chronic active hepatitis. This may be a further, previously undescribed systemic manifestation of Alström di

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400408

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

年代:1991

数据来源: WILEY

摘要:

AbstractAutosomal dominant adult‐onset polycystic kidney disease (ADPKD) is estimated to have an incidence of 1/1,000 and accounts for approximately 10% of all end‐stage renal disease in the United States. While relatives are attractive as renal donors due to their availability and the improved transplant success associated with living‐related donors, they may coincidentally be at risk for ADPKD. Accurate presymptomatic testing for at‐risk potential donors is critical for both the donor and the recipient. We report here 2 families in which presymptomatic testing for ADPKD was accomplished by DNA linkage analysis on several potential renal donors prior to transplant. This resulted in the protection of both donors and recipients by preventing the transplantation of a kidney affected by ADPKD. Thorough counseling prior to DNA analysis (including discussion of accuracy and possible testing outcomes of presymptomatic diagnosis of ADPKD, diagnosis of noncarrier status, false paternity, and noninformative study) was essential to provide informed consent and preserve confidentiality within the family. Confidentiality for potential donors found presymptomatically to be affected (with a 94% or greater probability) was especially difficult to m

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400409

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

年代:1991

数据来源: WILEY

摘要:

AbstractA newborn infant with the polyasplenia sequence, intrauterine growth retardation, cutaneous nevi, and minor anomalies was found to have mosaicism for ring chromosome 7. This patient's anomalies are markedly different from those of previous patients reported with this cytogenetic anomaly.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400410

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe concept ofuniparental disomy—the presence of a chromosome pair derived solely from one parent in a diploid offspring—was introduced in 1980 as a probable consequence of the high rate of germ cell aneuploidy in man, and has now been convincingly demonstrated through molecular analyses in several families. A most likely mechanism for the production of uniparental disomy is the chance reunion, and complementation, of 2 gametes aneuploid for the same chromosome member; uniparental disomy could also occur through other mechanisms including postzygotic nonsegregation in a trisomic conceptus.Uniparental dlsomy may result inisodisomy, i.e., homozygosity of a series of contiguous alleles in a pair of homologues. The presence and degree of isodisomy in an offspring depend in turn on the occurrence, timing, and extent of the meiotic recombination that had occurred in the chromosome pair of the disomic gamete involved.Uniparental disomy with or without isodisomy can explain a number of unusual observations, such as the unexpected pattern of transmission of a genetic disorder. The two may be associated with an imprinting effect to produce pathological phenotypes, as has been observed in the mouse, and may be the basis for a number of syndromes of as yet unclear cause.The evidence for uniparental disomy, isodisomy, and imprinting in man is reviewed, and strategies for their detection presen

ISSN:0148-7299    

DOI:10.1002/ajmg.1320400411

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

年代:1991

数据来源: WILEY