RESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is characterised by weakness and atrophy of the facial and shoulder girdle muscles. The FSHD phenotype segregates as an autosomal dominant trait and is caused by a deletion of an integral number of 3.3 kilobase pair (kb) repeat units on chromosome 4q35. Haplotype and Southern blot analyses of chromosome 4 resulted in the detection of two BlnI resistant deletion fragments, of 24 kb and 34 kb respectively, in a single individual from a South African FSHD family. The patient had moderate facial weakness and marked winging and high-riding of the scapulae with prominent pectoral and proximal arm muscle atrophy and weakness. Quadriceps and anterior tibial muscles were weak and the patient had bilateral foot drop. Although none of his children were symptomatic yet and only two showed very mild clinical signs, one had inherited the 24 kb deletion fragment, while the other two had the 34 kb deletion fragment. Molecular analysis conclusively identified the first compound heterozygous case in the South African FSHD population. However, in accordance with other studies of compound heterozygotes and clinical findings, no direct correlation between the clinical severity of this patient and the number of deletion fragments was observed.
Assuntos
Cromossomos Humanos Par 4/genética , Deleção de Genes , Heterozigoto , Distrofia Muscular Facioescapuloumeral/etnologia , Distrofia Muscular Facioescapuloumeral/genética , Desoxirribonuclease EcoRI/genética , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , África do SulAssuntos
DNA/análise , DNA/genética , Distrofia Muscular Facioescapuloumeral/diagnóstico , Distrofia Muscular Facioescapuloumeral/genética , Mutação/genética , Reação em Cadeia da Polimerase/normas , Alelos , Povo Asiático/genética , Cromossomos Humanos Par 4/genética , Análise Mutacional de DNA/economia , Análise Mutacional de DNA/métodos , Análise Mutacional de DNA/normas , Diagnóstico Precoce , Genótipo , Humanos , Repetições de Microssatélites/genética , Distrofia Muscular Facioescapuloumeral/etnologia , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Fatores de Tempo , População Branca/genéticaRESUMO
OBJECTIVE: To investigate the D4Z4 repeats on chromosome 4q35 in normal individuals in Shanghai and analysis the polymorphism of the D4Z4 locus. METHODS: The length of D4Z4 repeats on chromosome 4q35 in 191 normal individuals in Shanghai was determined by pulsed-field gel electrophoresis and Southern blotting after double digestion with Eco RI and Bln I. The number of short D4Z4 repeats was counted after partial digestion with Kpn I. RESULTS: Among 191 normal individuals in Shanghai, seventeen showed the size of D4Z4 fragments ranged from 22 to 34 kb, i.e. 8.9% of individuals had fewer numbers of D4Z4 repeats. Of these 17 individuals, sixteen showed the short D4Z4 fragment on chromosome 4q35, and one low D4Z4 fragment was correlated to 4q35--> 10q26 translocation. CONCLUSION: The frequency of individuals having fewer numbers of D4Z4 repeats on chromosome 4q35 in Shanghai population is higher than that in Caucasian population although the short D4Z4 fragment on chromosome 4q35 is associated with facioscapulohumeral muscular dystrophy. These findings suggest that other factors may also contribute to facioscapulohumeral muscular dystrophy.
Assuntos
Distrofia Muscular Facioescapuloumeral/genética , Polimorfismo Genético , Sequências de Repetição em Tandem/genética , Povo Asiático/genética , Southern Blotting , China , Cromossomos Humanos Par 4/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Ligação Genética , Humanos , Masculino , Distrofia Muscular Facioescapuloumeral/etnologia , LinhagemRESUMO
Current studies of facioscapulohumeral muscular dystrophy (FSHD) are confined to the white population. The authors surveyed 110 healthy individuals and 27 families with FSHD including 55 patients and 74 relatives by pulsed-field gel electrophoresis. The authors report the characteristics of translocation and genotype-phenotype correlation, and their results indicate 4q to 10q translocation contributes to the occurrence of de novo mutation. This leads to a more severe phenotype in the Chinese population comparing to EcoRI allele sizes and the intersexual difference.
Assuntos
Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 4/genética , Distrofia Muscular Facioescapuloumeral/etnologia , Polimorfismo de Fragmento de Restrição , Translocação Genética , Adolescente , Adulto , Alelos , Criança , China/epidemiologia , Cromossomos Humanos Par 10/ultraestrutura , Cromossomos Humanos Par 4/ultraestrutura , Análise Mutacional de DNA , Desoxirribonuclease EcoRI , Desoxirribonucleases de Sítio Específico do Tipo II , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Humanos , Masculino , Distrofia Muscular Facioescapuloumeral/genética , Linhagem , Fenótipo , Deleção de Sequência , Fatores Sexuais , Transcrição GênicaRESUMO
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by the weakness of facial, shoulder-girdle and upper arm muscles. Most patients with FSHD have fewer numbers of tandem repeated 3.3-kb KpnI units on chromosome 4q35. Chromosome 10q26 contains highly homologous KpnI repeats, and inter-chromosomal translocation has been reported. METHODS: To clarify the influence on the deletion of the repeats, we surveyed three different ethnic populations and FSHD patients using the BglII/BlnI dosage test. RESULTS: The frequency of translocation in 153 Japanese, 124 Korean, 114 Chinese healthy individuals and 56 Japanese 4q35-FSHD patients were 27.5%, 29.8%, 19.3%, and 32.1%, respectively. The ratio of '4 on 10' (trisomy and quatrosomy of chromosome 4) was higher than that of '10 on 4' (nullsomy and monosomy of chromosome 4) in all populations. CONCLUSIONS: The inter-chromosomal exchange was frequently observed in all four populations we examined, and no significant difference was observed between healthy and diseased groups.
