Abstract:
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.
摘要:
腰腿型肌营养不良症2C型(LGMD2C)被认为是儿童期发作的肌营养不良症的严重形式之一。SGCG基因中创始人突变的地理分布对某些人群中LGMD2C的流行具有显著影响。这项研究的目的是证实c.787G>A(p。SGCG基因中的E263K)突变是波多黎各西班牙裔中的基础突变,并表征相关的临床和免疫组织化学表型。对SGCG基因内部(D13S232)和侧翼(D13S175,D13S292,D13S787,D13S1243,D13S283)的六个多态微卫星标记进行了基因分型。在至少两名受试者中观察到维持行走至生命的第二个十年。骨骼肌的免疫染色表明在所有受影响的受试者中不存在γ-肌聚糖。两个标记,D13S232和D13S292提供了大量信息,并证实了所有四个家族都具有突变等位基因的单倍型。我们的发现证实,SGCG基因中的E263K错义突变是波多黎各裔西班牙裔的创始人突变。可以看到与这种突变相关的缓慢进展的疾病过程与长时间的步行保存有关,为表型变异性提供证据。