Huang Hao, Chen Yaqin, Jin Jieyuan, Du Ran, Tang Ke, Fan Liangliang, Xiang Rong
Department of Nephrology, Xiangya Hospital Central South University, Changsha, China.
Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China.
J Gene Med. 2022 Jan;24(1):e3390. doi: 10.1002/jgm.3390. Epub 2021 Oct 15.
Hypertrophic cardiomyopathy (HCM) is a hereditary disease manifested by a thickened ventricular wall. Cysteine and glycine-rich protein 3 (CSRP3), the gene encoding muscle LIM protein, is important for initiating hypertrophic gene expression. The mutation of CSRP3 causes dilated cardiomyopathy or HCM.
In the present study, we enrolled a Chinese family with HCM across three generations. Whole-exome sequencing (WES) was performed in the proband to detect the candidate genes of the family. Sanger sequencing was performed for mutational analysis and confirmation of cosegregation.
Through histopathological and imaging examinations, an obvious left ventricular hypertrophy was found in the proband. After WES data filtering, bioinformatic prediction and co-segregation analysis, a nonsense mutation (NM_003476.5:c.364C>T; NP_003467.1:p.Arg122*) of CSRP3 was identified in this family. This variant was predicted to be disease-causing and resulted in a truncated protein.
This is the first HCM family case of CSRP3 (p.Arg122*) variation in Asia. The finding here not only contributes to the genetic diagnosis and counseling of the family, but also provides a new case with detailed phenotypes that may be caused by the CSRP3 variant.
肥厚型心肌病（HCM）是一种以心室壁增厚为特征的遗传性疾病。富含半胱氨酸和甘氨酸的蛋白3（CSRP3），即编码肌肉LIM蛋白的基因，对于启动肥厚基因表达很重要。CSRP3的突变会导致扩张型心肌病或HCM。
在本研究中，我们纳入了一个三代均患有HCM的中国家庭。对先证者进行全外显子组测序（WES）以检测该家庭的候选基因。进行Sanger测序以进行突变分析和共分离确认。
通过组织病理学和影像学检查，在先证者中发现明显的左心室肥厚。经过WES数据过滤、生物信息学预测和共分离分析，在该家庭中鉴定出CSRP3的一个无义突变（NM_003476.5:c.364C>T；NP_003467.1:p.Arg122*）。该变异被预测为致病突变，并导致截短蛋白。
这是亚洲首例报道的CSRP3（p.Arg122*）变异导致的HCM家系病例。本研究结果不仅有助于该家庭的遗传诊断和遗传咨询，还提供了一个可能由CSRP3变异导致的具有详细表型的新病例。
