A slowly progressive form of limb-girdle muscular dystrophy type 2C associated with founder mutation in the SGCG gene in Puerto Rican Hispanics
A slowly progressive form of limb-girdle muscular dystrophy type 2C associated with founder mutation in the SGCG gene in Puerto Rican Hispanics
复制标题
DOI：
10.1002/mgg3.125
复制
发表时间：
2015-03-01
影响因子：
2
通讯作者：
Mendell, Jerry R.
中科院分区：
文献类型：
--
作者：
Al-Zaidy, Samiah A.;Malik, Vinod;Mendell, Jerry R.
肢带型肌营养不良症2C型（LGMD 2C）被认为是儿童期发病的肌营养不良症的严重形式之一。SGCG基因创始者突变的地理分布对某些人群中LGMD 2C的患病率有显著影响。本研究的目的是证实SGCG基因中的c.787G>A（p.E263K）突变是波多黎各西班牙裔人中的创始突变的假设，并描述相关的临床和免疫组化表型。对4名不相关的波多黎各LGMD 2C患者进行SGCG基因内部（D13 S232）和侧翼（D13 S175，D13 S292，D13 S787，D13 S1243，D13 S283）的6个多态性微卫星标记的基因分型。在至少两名受试者中观察到生命的第二个十年的保护。骨骼肌的免疫染色显示所有受影响的受试者中没有c-肌聚糖。两个标记，D13 S232和D13 S292，是高度信息化的，并证实所有四个家庭共享的突变等位基因的单倍型。我们的研究结果证实，在SGCG基因E263 K错义突变是一个创始人在波多黎各西班牙裔突变。可以看到与这种突变相关的缓慢进展的病程和延长的Ampectin保存，为表型变异提供了证据。
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 c-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.