RESUMEN
X-linked myotubular myopathy (XLMTM; MIM# 310400) is a severe congenital muscle disorder caused by mutations in the MTM1 gene. This gene encodes a dual-specificity phosphatase named myotubularin, defining a large gene family highly conserved through evolution (which includes the putative anti-phosphatase Sbf1/hMTMR5). We report 29 mutations in novel cases, including 16 mutations not described before. To date, 198 mutations have been identified in unrelated families, accounting for 133 different disease-associated mutations which are widespread throughout the gene. Most point mutations are truncating, but 26% (35/133) are missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affect 17% of the patients, and a total of 21 different mutations were found in several independent families. The frequency of female carriers appears higher than expected (only 17% are de novo mutations). While most truncating mutations cause the severe and early lethal phenotype, some missense mutations are associated with milder forms and prolonged survival (up to 54 years).
Asunto(s)
Mutación , Miopatías Estructurales Congénitas/genética , Proteínas Tirosina Fosfatasas/genética , Cromosoma X , Empalme Alternativo , Elementos Transponibles de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Familia de Multigenes , Mutación Missense , Miopatías Estructurales Congénitas/mortalidad , Polimorfismo Genético , Proteínas Tirosina Fosfatasas no Receptoras , Eliminación de Secuencia , Análisis de SupervivenciaRESUMEN
In a joint analysis of nuclear (allozyme) and mitochondrial markers (sequence and restriction fragment length polymorphism (RFLP) analysis of the 12S and 16S genes), five genetically distinct groups of the Austropotamobius pallipes Lereboullet species complex were detected in the Alpine region. The geographical distribution of these evolutionary lineages coincided largely with several taxa (A.p. pallipes, A. berndhauseri, A.(p.) italicus) formerly defined on the basis of morphological characters. A low level of genetic variability was found within these lineages. For some populations, the combination of the two markers gave additional information about the likelihood of their natural or artificial origin. A hybrid zone was detected between A.p. pallipes and A. berndhauseri in the Lake Geneva area. The mosaic distribution of the five evolutionary lineages indicated that conservation efforts should be aimed at the level of local populations.