Allamand V, Broux O, Bourg N, Richard I, Tischfield J A, Hodes M E, Conneally P M, Fardeau M, Jackson C E, Beckmann J S
Généthon, Evry, France.
Hum Mol Genet. 1995 Mar;4(3):459-63. doi: 10.1093/hmg/4.3.459.
Limb-girdle muscular dystrophy (LGMD) is a hereditary myopathy presenting clinical and genetic heterogeneity. In 1991, a recessive form (LGMD2A) was linked to chromosome 15q in a genetic isolate from the Isle of La Réunion. Confirmation of this localization was subsequently reported in Brazilian and northern Indiana Amish pedigrees. Here we report the exclusion of the LGMD2A locus in six Amish kindreds from southern Indiana that are related by multiple consanguineous links to the same northern Indiana families in which the involvement of the chromosome 15 locus was previously demonstrated. These findings indicate unexpected genetic heterogeneity of LGMD in an Indiana Amish isolate. Furthermore, genetic analyses also ruled out the possible involvement of the chromosome 2 locus recently described (LGMD2B), thus demonstrating that a mutation within at least one additional locus leads to this condition. Several candidate genes putatively involved in neuromuscular disorders were also excluded.
肢带型肌营养不良症（LGMD）是一种具有临床和遗传异质性的遗传性肌病。1991年，一种隐性形式（LGMD2A）在留尼汪岛的一个遗传隔离群体中与15号染色体q臂连锁。随后在巴西和印第安纳州北部的阿米什人谱系中报告了这一定位的证实情况。在此，我们报告在印第安纳州南部的六个阿米什人家族中排除了LGMD2A基因座，这些家族通过多重近亲关系与印第安纳州北部的同一家庭相关，而之前已证明15号染色体基因座与这些北部印第安纳州家庭的发病有关。这些发现表明印第安纳州阿米什人隔离群体中LGMD存在意外的遗传异质性。此外，遗传分析还排除了最近描述的2号染色体基因座（LGMD2B）可能的参与，从而证明至少一个其他基因座内的突变导致了这种疾病。几个推测与神经肌肉疾病有关的候选基因也被排除。
