摘要:

AbstractCases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450113

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe describe an infant with a lumber meningomyelocele and other congenital anomalies and a de novo deletion of 2q36 with a nonmosaic karyotype 46,XX,del(2)(q36). © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450114

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe report on 14 patients with partial deletions of chromosome 13q. These patients exhibit a wide spectrum of phenotypes. Deletions limited to proximal bands q13–q31 are associated with growth retardation but not with major malformations. We review the literature since 1975 and summarize 13q deletion cases which have a phenotype involving one or more major malformations and mental retardation. Analysis of the breakpoints of these cases, as well as those reported by us, supports the hypothesis that only deletions involving at least part of band q32 are associated with major malformations and digital abnormalities. Patients with more distal deletions have severe mental retardation but do not have major malformations or growth retardation. A group of patients in whom the breakpoint is stated to be within q32 has had an intermediate phenotype. This suggests that it may be possible to define subregions within q32 whose deletion is associated with particular developmental defects. © 1993 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450115

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

年代:1993

数据来源: WILEY

摘要:

AbstractAs part of a detailed study of limb defects and associated patterns of congenital malformations, cases with lower limb deficiencies were analysed separately. We identified a total of 130 cases with deficiencies of the lower limbs without defects of the upper limbs. This gives an incidence of 1.07/10,000 livebirths, or 1/9,337 for this group of limb defects. Most common were femur deficiencies and deficiencies of the foot. A preponderance of males was found in the group of transverse defects of the leg (fibula/tibia deficiencies) and central axis deficiencies, while females had significantly more often longitudinal tibia defects and preaxial ray defects. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450116

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe report on a 19‐month‐old girl with a derivative chromosome 9 and a recombinant chromosome 12 resulting from a maternal balanced complex rearrangement involving chromosomes 8, 9, and 12. The karyotype of the phenotypically normal mother was 46,XX,t(8;12) (9;12) (8qter→8p23::12q12→12q15::9q32→9qter;9pter→9q32::12q15→12qter;12pter→12q12::8p23→8pter). The child's karyotype was 46,XX,−9,−12, +der(9) (9pter→9q32::12q15→12qter),+rec(12) (12pter→12q15::9q32→9qter) mat. The child had severe growth retardation, minor anomalies including trigonocephaly, hypertelorism, broad nasal root, apparently low‐set and posteriorly angulated ears, triangular face, pectus carinatum, clinodactyly of fifth fingers, and almost normal psychomotor development. To the best of our knowledge, there have been only 3 previous reports of recombination derived from parental complex chromosome rearrangements. In the recombination products, the chromosomes were apparently balanced and the offspring had no clinical abnormalities. The present case exhibited abnormalities and may have a submicroscopic aberration of 12q arising from crossing over during maternal meiotic pairing, although her chromosomes appeared to be b

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450117

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

年代:1993

数据来源: WILEY

摘要:

AbstractAmyotrophic lateral sclerosis (ALS) and parkinsonism‐dementia (PD) are neurological degenerative disorders that occur in three high incidence foci in the western Pacific: among the Chamorros of Guam and the Commonwealth of the Northern Marianas Islands, among Japanese on the Kii peninsula of Honshu Island, and among the Auyu and Jakai peoples of southern West New Guinea. Previous studies have implicated both genetic susceptibility and environmental risk factors in the causation and familial clustering of these disorders. The data analyzed consist of 2,026 individuals in nuclear families ascertained on Guam through two mechanisms: (1) nuclear families were included in the study if one or both parents in the family were affected with ALS or PD or both; and (2) a group of “controls” was selected by obtaining nuclear families where neither parent was affected and both had lived through the age of risk. Clinically, ALS and PD are two distinct disorders. However, preliminary analyses indicated that combining all three diagnoses into one affected diagnosis for genetic analyses (thereby assuming any genetic effect on susceptibility to the two disorders was due to the same genetic mechanism) was reasonable. An age, sex and birth cohort‐specific liability was defined and segregation analysis was performed under both logistic and normal models for this liability at the time of disease onset. Under either model, purely environmental, Mendelian dominant and Mendelian recessive hypotheses could be rejected, but a two‐allele additive major locus hypothesis could not be rejected. © 1993 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450118

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

年代:1993

数据来源: WILEY

摘要:

AbstractHereditary cutaneous malignant melanoma (HCMM) with or without atypical moles has been described in several large kindreds worldwide. Despite numerous studies of these kindreds, the gene or genes responsible for this disorder has not yet been identified. Cytogenetic and molecular studies of melanoma tumor tissue and cell lines suggest that a gene involved in the pathogenesis of malignant melanoma lies on chromosome 9p. We describe a woman with atypical moles and multiple primary melanomas, who lacks a family history of HCMM, and, has a de novo constitutional unbalanced reciprocal translocation involving the short arms of chromosomes 5 and 9 with a cytogenetically visible deletion of 5p or 9p: [46,XX,‐5,‐9, +der(5)t(5;9) (p13.3 or 14.2;p13.3 or 21.2), +der(9)t(5;9)]. This finding supports the hypothesis that a gene predisposing to HCMM lies on the short arm of chromosome 9. © 1993 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450119

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

年代:1993

数据来源: WILEY

摘要:

AbstractCyclic AMP production was studied in platelets from 31 patients with fragile X syndrome, 16 patients with mental retardation, 4 patients with autistic disorder, and 57 control individuals. 1‐isobutyl‐3‐methylxanthine (IBMX) was used to inhibit phosphodiesterase; prostaglandin E1(PGE1), to stimulate cAMP production via a receptor‐dependent mechanism, and forskolin (FSK), to directly activate the catalytic subunit. Cyclic AMP production in IBMX, PGE1+ IBMX, and FSK + IBMX was 50% (P<0.05), 65% (P=0.001), and 53% (P= 0.001), respectively, in fragile X platelets relative to controls. Cyclic AMP production was not statistically different from controls in patients with mental retardation or autistic disorder. There was no effect of age or sex on cAMP production. Dose response curves suggested that abnormal cAMP production was due to diminished maximal response rather than altered potency of stimulating agents. The data presented here demonstrate that diminished cAMP production exists in platelets from patients with fragile X syndrome. Thus, defective functioning of cAMP‐mediated regulatory signalling pathways in fragile X brain may contribute to the mental deficiency in these patients. © 1993 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450120

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe National Neurofibromatosis Foundation International Database is a system for collecting comprehensive information on the clinical manifestations and natural history of neurofibromatosis. Data are entered into personal computers at participating centres and are pooled at the Central Database and coordinating centre in Vancouver, Canada. The system includes special mechanisms to assure consistency among centres and to maintain patient confidentiality. The database is designed to foster collaborative clinical and molecular genetic research in many aspects of neurofibromatosis. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450121

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

年代:1993

数据来源: WILEY

摘要:

AbstractCharcot‐Marie‐Tooth disease type 1A (CMT1A) was recently demonstrated to be associated with a large DNA duplication in 17p11.2p12. The gene for neurofibromatosis type 1 (NF1) or von Recklinghausen disease maps to 17q11.2. We have identified 2 unrelated patients who were diagnosed with both CMT1 and NF1. Molecular analysis of these patients demonstrated the presence of the CMT1A duplication and inheritance of this DNA rearrangement from a parent affected with CMT. Analysis of genomic DNA isolated from the neurofibroma removed from one of these patients showed the same 500 kbSacII junction fragment associated with the CMT1A duplication that was found in genomic DNA isolated from the blood. These results lend further support to the hypothesis that the CMT1A duplication is a stable DNA rearrangement. In addition, the molecular analysis of these 2 patients suggests that 2 common autosomal dominant conditions (CMT1 and NF1) can occur in the same individual, not because of an underlying single molecular defect, but rather, secondary to a chance phenomenon. © 1993 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320450122

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

年代:1993

数据来源: WILEY