Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio ; Department of Pediatrics and Neurology, The Ohio State University Columbus, Ohio.
Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio.
Mol Genet Genomic Med. 2015 Mar;3(2):92-8. doi: 10.1002/mgg3.125. Epub 2015 Jan 8.
Limb-girdle muscular dystrophy type 2C (LGMD2C) is considered one of the severe forms of childhood-onset muscular dystrophy. The geographical distribution of founder mutations in the SGCG gene has a prominent effect on the prevalence of LGMD2C in certain populations. The aim of this study was to confirm the hypothesis that the c.787G>A (p.E263K) mutation in the SGCG gene is a founder mutation among Puerto Rican Hispanics and to characterize the associated clinical and immunohistochemical phenotype. Genotyping of six polymorphic microsatellite markers internal to (D13S232) and flanking (D13S175, D13S292, D13S787, D13S1243, D13S283) the SGCG gene was performed on four unrelated Puerto Rican patients with LGMD2C. Preserved ambulation to the second decade of life was observed in at least two subjects. Immunostaining of skeletal muscle demonstrated absence of γ-sarcoglycan in all affected subjects. Two markers, D13S232 and D13S292, were highly informative and confirmed that all four families share the haplotype of the mutant allele. Our findings confirm that the E263K missense mutation in the SGCG gene is a founder mutation in Puerto Rican Hispanics. A slowly progressive disease course with prolonged preservation of ambulation can be seen in association with this mutation, providing evidence for phenotypic variability.
肢带型肌营养不良 2C 型（LGMD2C）被认为是儿童期起病的严重型肌营养不良症之一。SGCG 基因突变的地理分布对某些人群中 LGMD2C 的患病率有显著影响。本研究旨在验证假设，即 SGCG 基因中的 c.787G>A（p.E263K）突变是波多黎各西班牙裔人群中的一个起始突变，并对相关的临床和免疫组化表型进行特征描述。对四名无亲缘关系的患有 LGMD2C 的波多黎各患者进行了六个位于 SGCG 基因内部（D13S232）和侧翼（D13S175、D13S292、D13S787、D13S1243、D13S283）的多态性微卫星标记的基因分型。至少有两名患者在第二十年仍能保持独立行走。骨骼肌免疫组化显示所有受影响的患者均缺乏γ-连接蛋白。两个标记物 D13S232 和 D13S292 具有高度信息量，证实了所有四个家系均携带突变等位基因的单体型。我们的研究结果证实了 SGCG 基因中的 E263K 错义突变是波多黎各西班牙裔人群中的一个起始突变。与该突变相关的疾病呈缓慢进行性进展，且步行能力可长期维持，这为表型的变异性提供了证据。
