Chen Zuzhi, Ren Zhixia, Mei Wenli, Ma Qiankun, Shi Yingying, Zhang Yuanxing, Li Shujian, Xiang Li, Zhang Jiewen
Department of Neurology, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China.
BMC Med Genet. 2017 Jun 5;18(1):63. doi: 10.1186/s12881-017-0424-5.
In the present study, a novel mutation in exon 46 at codon 2304 (G2304R) of the SYNE1 gene is described in a Chinese family (proband, mother, and sister) with Emery-Dreifuss muscular dystrophy-like, which clinically manifests as muscle weakness, muscle atrophy, joint contracture, and without significant cardiac abnormalities.
Clinical examination and neuroimaging of the captured target region and high-throughput sequencing were performed in a family of four generations. Muscle changes were evaluated using magnetic resonance imaging and muscle biopsies.
Target region capture sequencing yielded a novel missense mutation in codon 2304 (G2304R), which is a heterozygous A to G point mutation at position 6910 (c.6910A > G) in exon 46 of SYNE1 leading to a glycine-to-arginine substitution (p.Gly2304Arg). The results were also identified by Sanger sequencing in three family members but not in the other three unaffected family members and 100 control subjects.
This mutation is probably pathogenic and is the first of its kind reported in a familial Emery-Dreifuss muscular dystrophy-like.
在本研究中，一个患有埃默里-德赖富斯样肌营养不良症的中国家庭（先证者、母亲和妹妹）中描述了SYNE1基因第46外显子第2304密码子（G2304R）处的一种新突变，临床表现为肌肉无力、肌肉萎缩、关节挛缩，且无明显心脏异常。
对一个四代家庭进行了临床检查、捕获目标区域的神经影像学检查和高通量测序。使用磁共振成像和肌肉活检评估肌肉变化。
目标区域捕获测序在第2304密码子处产生了一个新的错义突变（G2304R），这是SYNE1基因第46外显子第6910位（c.6910A>G）的杂合A到G点突变，导致甘氨酸被精氨酸取代（p.Gly2304Arg）。三名家庭成员的桑格测序结果也证实了这一结果，但另外三名未受影响的家庭成员和100名对照受试者中未发现该结果。
这种突变可能具有致病性，是家族性埃默里-德赖富斯样肌营养不良症中首次报道的此类突变。
