Evidence for genetic heterogeneity supports clinical differences in congenital myasthenic syndromes.
Evidence for genetic heterogeneity supports clinical differences in congenital myasthenic syndromes.
复制标题
遗传异质性的证据支持先天性肌无力综合征的临床差异。
DOI：
10.1159/000022824
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发表时间：
1998
期刊：
影响因子：
1.8
通讯作者：
Pericak-Vance,MA
中科院分区：
文献类型：
--
作者：
Menold,MM;Sadeh,M;Lennon,F;Blatt,I;Goldhammer,Y;Yamaoka,LH;Vance,JM;Pericak-Vance,MA
先天性肌无力综合征（CMS）定义了一组不同的疾病，所有这些疾病都会损害神经肌肉传递。症状可以在出生时出现，也可以在儿童时期出现，严重程度不等。常染色体显性和隐性形式都存在，并且已经描述了许多临床亚型。许多CMS病例的原因可以追溯到乙酰胆碱受体（AChR）亚基基因的突变，以前定位于2号和17号染色体。最近，CMS的另一种形式被称为家族性婴儿肌无力（familial infantile myasthenia，简称FMG），与染色体17 p有关。这种基因还没有被发现。我们检查了来自5个伊朗犹太血统家庭（6个受影响的个体）的DNA，这些家庭被诊断患有表型独特的CMS。其中四个家族是近亲，所有家族都来自同一地理区域，因此它们很可能携带相同的祖先CMS突变。我们检查了这些家庭的连锁区域的2号和17号染色体上含有AChR亚基基因，并在17 p的区域，其中AChR是本地化。我们的数据排除了与这些区域的联系，表明CMS患者的临床差异与基因座异质性相关，不同基因的缺陷是这些患者CMS的原因。
Congenital myasthenic syndromes (CMS) define a diverse group of disorders, all of which compromise neuromuscular transmission. Symptoms can be present at birth or appear during childhood, and can range in severity. Both autosomal dominant and recessive forms exist, and a number of clinical subtypes have been described. The cause of many cases of CMS has been traced to mutations in the genes for the acetylcholine receptor (AChR) subunits, previously mapped to chromosomes 2 and 17. Recently, an additional form of CMS known as familial infantile myasthenia (FIM) was linked to chromosome 17p. The gene for FIM has not yet been identified. We examined the DNA from 5 families of Iranian Jewish origin (6 affected individuals) who have been diagnosed with a phenotypically unique form of CMS. Four of the families are consanguinous, and all families originate from the same geographical region, thus it is highly likely that they would carry the same ancestral CMS mutation. We examined these families for linkage to the regions on chromosomes 2 and 17 containing the AChR subunit genes, and to the region on 17p to which FIM was localized. Our data excludes linkage to these regions, suggesting that the clinical differences seen among patients with CMS correlate with locus heterogeneity, and that a defect in a different gene is responsible for the CMS in these patients.