RESUMO
Dysferlin encoding gene (DYS) is mutated in the autosomal recessive disorders Miyoshi myopathy, Limb Girdle Muscular Dystrophy type 2B (LGMD2B) and distal anterior compartment myopathy, causing dysferlin deficiency in muscle biopsy. Three ethnic clusters have previously been described in Dysferlinopathy: the Libyan Jewish population originating in the area of Tripoli, Italian and Spanish populations. We report another cluster of this muscular dystrophy in Israel among Jews of the Caucasus region. A genomic analysis of the dysferlin coding sequence performed in patients from this ethnic group, who demonstrated an absence of dysferlin expression in muscle biopsy, revealed a homozygous frameshift mutation of G deletion at codon 927 (2779delG) predicting a truncated protein and a complete loss of functional protein. The possible existence of a founder effect is strengthened by our finding of a 4% carrier frequency in this community. These findings are important for genetic counseling and also enable a molecular diagnosis of LGMD2B in Jews of the Caucasus region.
Assuntos
Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Proteínas Musculares/genética , Doenças Musculares/etnologia , Doenças Musculares/genética , Mutação/genética , Adolescente , Adulto , Ásia Ocidental/etnologia , Transtornos Cromossômicos/genética , Análise Mutacional de DNA , Disferlina , Feminino , Efeito Fundador , Mutação da Fase de Leitura/genética , Deleção de Genes , Genes Recessivos/genética , Testes Genéticos , Geografia , Heterozigoto , Humanos , Judeus/etnologia , Judeus/genética , Masculino , Doenças Musculares/metabolismoRESUMO
Oculopharyngeal muscular dystrophy (OPMD) is considered frequent among French Canadians. Our previous observations suggested it is common also among the Jews originating from Bukhara in Uzbekistan, many of whom are now living in Israel. One hundred and seventeen OPMD patients were identified in a population of 70,000 people of Bukharian descent, resulting in a calculated minimal prevalence of 1:600. In all but three families age dependent autosomal dominant inheritance was documented. There is some evidence for genetic anticipation. Three young, severely ill, patients from two different families may be homozygotes, their parents being both affected. Bukhara Jews present the second largest known cluster and the prevalence is the highest in the world. The existence of very large families, intermarriage among carriers and probably homozygote offspring may be useful for genetic studies. A 'founder effect' may explain the high prevalence of OPMD in this population.
