Weiler T, Greenberg C R, Nylen E, Morgan K, Fujiwara T M, Crumley M J, Zelinski T, Halliday W, Nickel B, Triggs-Raine B, Wrogemann K
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
Am J Med Genet. 1997 Oct 31;72(3):363-8. doi: 10.1002/(sici)1096-8628(19971031)72:3<363::aid-ajmg22>3.0.co;2-q.
Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of disorders affecting primarily the shoulder and pelvic girdles. Autosomal dominant and recessive forms have been identified; 8 have been mapped and 1 more has been postulated on the basis of exclusion of linkage. An autosomal recessive muscular dystrophy was first described in 1976 in the Hutterite Brethren, a North American genetic and religious isolate [Shokeir and Kobrinsky, 1976; Clin Genet 9:197-202]. In this report, we discuss the results of linkage analysis in 4 related Manitoba Hutterite sibships with 21 patients affected with a mild autosomal recessive form of LGMD. Because of the difficulties in assigning a phenotype in some asymptomatic individuals, stringent criteria for the affected phenotype were employed. As a result, 7 asymptomatic relatives with only mildly elevated CK levels were assigned an unknown phenotype to prevent their possible misclassification. Two-point linkage analysis of the disease locus against markers linked to 7 of the known LGMD loci and 3 other candidate genes yielded lod scores of < or = -2 at theta = 0.01 in all cases and in most cases at theta = 0.05. This suggests that there is at least 1 additional locus for LGMD.
肢带型肌营养不良症（LGMD）是一组主要影响肩部和骨盆带的异质性疾病。已确定常染色体显性和隐性形式；8个致病基因已被定位，基于连锁排除又推测出1个。1976年首次在哈特派兄弟会（北美一个具有遗传隔离性的宗教群体）中描述了一种常染色体隐性肌营养不良症[绍凯尔和科布林斯基，1976年；《临床遗传学》9：197 - 202]。在本报告中，我们讨论了对4个相关的曼尼托巴哈特派同胞系谱进行连锁分析的结果，这些系谱中有21名患者患有轻度常染色体隐性形式的LGMD。由于在一些无症状个体中确定表型存在困难，因此对受累表型采用了严格标准。结果，7名仅肌酸激酶（CK）水平轻度升高的无症状亲属被归为未知表型，以防止可能的错误分类。对疾病位点与7个已知LGMD位点及其他3个候选基因相关的标记进行两点连锁分析，在所有病例中，当θ = 0.01时，对数优势分数（lod score）≤ -2，在大多数病例中，当θ = 0.05时也是如此。这表明LGMD至少还有1个额外的致病位点。
