Khadilkar Satish V, Chaudhari Chetan R, Dastur Rashna S, Gaitonde Pradnya S, Yadav Jayendra G
Department of Neurology, Grant Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India.
Centre for Advanced Molecular Diagnostics in Neuromuscular Disorders (CAMDND), Mumbai, Maharashtra, India.
Ann Indian Acad Neurol. 2016 Jan-Mar;19(1):108-11. doi: 10.4103/0972-2327.175435.
Diagnostic evaluation of limb-girdle muscular dystrophy type 2A (LGMD2A) involves specialized studies on muscle biopsy and mutation analysis. Mutation screening is the gold standard for diagnosis but is difficult as the gene is large and multiple mutations are known. This study evaluates the utility of two known founder mutations as a first-line diagnostic test for LGMD2A in the Agarwals.
The Agarwals with limb-girdle muscular dystrophy (LGMD) phenotype were analyzed for two founder alleles (intron 18/exon 19 c.2051-1G>T and exon 22 c.2338G>C). Asymptomatic first-degree relatives of patients with genetically confirmed mutations and desirous of counseling were screened for founder mutations.
Founder alleles were detected in 26 out of 29 subjects with LGMD phenotype (89%). The most common genotype observed was homozygous for exon 22 c.2338 G>C mutation followed by compound heterozygosity. Single founder allele was identified in two. Single allele was detected in two of the five asymptomatic relatives.
Eighty-nine percent of the Agarwals having LGMD phenotype have LGMD2A resulting from founder mutations. Founder allele analysis can be utilized as the initial noninvasive diagnostic step for index cases, carrier detection, and counseling.
2A型肢带型肌营养不良症（LGMD2A）的诊断评估涉及肌肉活检和突变分析等专门研究。突变筛查是诊断的金标准，但由于该基因较大且已知有多种突变，实施起来较为困难。本研究评估了两种已知的奠基者突变作为阿加瓦尔家族中LGMD2A一线诊断检测方法的效用。
对表现出肢带型肌营养不良（LGMD）表型的阿加瓦尔家族成员分析两种奠基者等位基因（内含子18/外显子19 c.2051-1G>T和外显子22 c.2338G>C）。对基因检测确认有突变且希望接受遗传咨询的患者的无症状一级亲属进行奠基者突变筛查。
29名表现出LGMD表型的受试者中有26名（89%）检测到奠基者等位基因。观察到的最常见基因型是外显子22 c.2338 G>C突变的纯合子，其次是复合杂合子。在两名受试者中鉴定出单个奠基者等位基因。在五名无症状亲属中的两名检测到单个等位基因。
89%表现出LGMD表型的阿加瓦尔家族成员患有由奠基者突变导致的LGMD-2A。奠基者等位基因分析可作为索引病例、携带者检测和遗传咨询的初始非侵入性诊断步骤。
