ISSN:0148-7299    

DOI:10.1002/ajmg.1320460102

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe majority of patients with Angelman syndrome and Prader‐Willi syndrome have a cytogenetic and molecular deletion of chromosome 15q11q13 with the primary difference being in the parental origin of deletion. Our current understanding of the cytogenetics and molecular genetics of these 2 clinically distinct syndromes will be discussed in this review. © 1993 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460103

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe report on cytogenetic and molecular analysis of 29 Angelman syndrome (AS) individuals ascertained in 1990 through the first National Angelman Syndrome Conference. High resolution GTG‐ and GBG‐banded chromosomes were studied. Standard molecular analysis with six 15q11q13 DNA sequences was used to analyze copy number and parental origin of 15q11q13. Concordance between molecular and cytogenetic data was excellent. The combind data showed that 23 of the 27 probands (85%) on whom we had definitive results have deletions of the chromosome 15q11q13 region. Two classes of deletion were detected molecularly: most patients were deleted for the 5 more proximal probes, but in 2 cases the deletion extended distally to include in sixth probe. In the 13 cases where the parental origin of the deleted chromosome 15 could be established, it was maternal. There were no cases of uniparental disomy. Cytological observations of the relative sizes of the heterochromatic regions of the short arm of chromosome 15 suggested that chromosomes with large heterochromatic blocks may be more prone tode novodeletion. © 1993 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460104

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

年代:1993

数据来源: WILEY

摘要:

AbstractClinical information has been obtained on 82 Angelman syndrome (AS) families in the UK. Each patient was examined by the author and a detailed clinical history taken. The findings of this study are presented. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460105

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

年代:1993

数据来源: WILEY

摘要:

AbstractAlthough Angelman (AS) and Prader‐Willi (PWS) syndromes are human genetic disorders with distinctly different developmental and neurobehavioural phenotypes, they both have abnormalities in inheritance of chromosome 15q11–q13. Whether AS or PWS arises depends on the parental origin of a deletion or uniparental disomy (the inheritance of 2 copies of a genetic locus from only one parent) for 15q11–q13. Normal development requires a genetic contribution for this genetic region from both a male and female parent. The dependence on parental origin implies that genes in human 15q11–q13 have distinct functions depending upon epigenetic, parent‐of‐origin differences, known as genomic imprinting. Here, I review the role of uniparental disomy and genomic imprinting in the pathogenesis of AS and PWS, and briefly discuss phenotype‐genotype correlations using candidate genes and mouse models, in particular for hypopigmentation. © 1993 W

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460106

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

年代:1993

数据来源: WILEY

摘要:

AbstractRecent improvements in magnetic resonance imaging techniques now allow the developing brain to be visualized in sufficient detail to perform “in vivo neuropathology.” In this study we compared the cortical morphology in six children with Angelman and four with Prader‐Willi syndrome. These two syndromes are of especial interest because, although they are both caused by deletions in the same region of chromosome 15, Angelman children are far more severely affected, and do not speak. We measured the length of the banks of the Sylvian fissure in a gapless series of thin sagittal images. Angelman children had a significantly larger proportion (75%) of anomalous fissures than the Prader‐Willi children (12%). Anomalous cortical growth could result from mistimed expression and recognition of macromolecules involved in axonal guidance, target recognition, and pruning. We hypothesize that misrouting of long projection axons may be related to the Sylvian fissure anomalies and the language disorder in Angelman syndrome. © 1993 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460107

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

年代:1993

数据来源: WILEY

摘要:

AbstractPersons with Angelman syndrome (AS) have mental retardation epilepsy, and a characteristic “puppet‐like” gait. Behaviorally, they are distinctive because they have no speech and have excessive laughter. A speech and communication evaluation of 7 persons with AS was performed to provide improved understanding of the speech deficit. Assessments included prelanguage and language development, oral motor abilities, and cognitive and social interaction skills. Results indicate that the typical lack of speech may not be due to mental retardation alone. Oral motor dyspraxia, and deficits in social interaction and attention were characteristic of AS and contributed to the lack of speech. © 1993 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460108

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

年代:1993

数据来源: WILEY

摘要:

AbstractChromosome region 15q is thought to contain one or more genes that are important for melanin pigment synthesis in the hair, skin, and eyes. Hypopigmentation has been identified in the Prader‐Willi (PWS) and Angelman (AS) syndromes. We have examined 6 individuals with AS to further characterize the pigment pattern in this condition. The age of the 5 girls and one boy ranged from 2.4 to 7.0 years. None has obvious albinism. Hair color ranged from light blond to brown. Skin was type I in 3 and type II in 3. Eye changes included nystagmus in 2, strabismus in 4, and reduced retinal pigment in 5. The mean hairbulb tyrosinase activity was 0.37 ± 0.44 pmol/hb/120 min for the individuals with AS, with a range of 0.00 to 1.13 (normal brown control 1.49 ± 0.79, normal blond control 1.50 ± 0.85). Electron microscopic examination of hairbulb melanocytes showed normal melansome and melanocyte architecture and number, but reduced melanin formation, with many stage II and III premelanosomes but few stage IV fully melanized melanosomes. Hypopigmentation characterized by light skin, reduced retinal pigment, low hairbulb tyrosinase activity, and incomplete melanization of melanosomes is part of the phenotype of AS, and is similar to that found in PWS. © 1993 Wiley‐Li

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460109

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe partial nucleotide sequence encoding the rod portion of the entire amino acid sequence of human smooth muscle myosin heavy chain (MHC) which corresponds to MYH11, according to Human Gene Mapping nomenclature, has been determined by cloning a complementary DNA (cDNA) and sequencing the cDNA (UMYHSM). Northen blot analysis with the UMYHSM fragment (4.3 Kb) showed that the smooth muscle MHC of the human umbilical artery is expressed in the human umbilical artery, bladder, esophagus and trachea. Southern blot analysis of human genomic DNA from human‐mouse or human‐Chinese hamster somatic cell hybrids demonstrated that the human smooth muscle MHC was mapped to human chromosome 16. Regional mapping of UMYHSM was performed using human cell lines with partial deletion and trisomy of chromosome 16. As a result, the human smooth muscle MHC gene segregated with 16p11‐q12. In situ hybridization of biotin‐labeled human smooth muscle MHC probe (UMYHSM fragment) to normal human metaphase chromosome independently showed that the human smooth muscle MHC gene (MYH11) is assigned to chromosome region 16q12. Analysis of early metaphase chromosomes showed that hybridization signals were in 16q12.1. In the human, although skeletal, cardiac, smooth muscle, and nonmuscle MHC genes are mapped to chromosomes 17, 14, 16 and 22, respectively, structural similarities of these MHC genes strongly suggest the common origin of these genes. © 1993 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460110

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe report on an infant girl born with complete trisomy 22 and left hemifacial microsomia, ear anomaly and limbal and epibulbar complex choristoma. Trisomy 22 was confirmed by prometaphase chromosome analysis and in situ hybridization. This patient extends the list of chromosome abnormalities associated with apparent Goldenhar sequence and emphasizes the importance of chromosome analysis in the investigation of patients with this condition. A detailed ophthalmopathological investigation is reported. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460111

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

年代:1993

数据来源: WILEY