An LMNA synonymous variant associated with severe dilated cardiomyopathy: Case report.
An LMNA synonymous variant associated with severe dilated cardiomyopathy: Case report.
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DOI：
10.1002/ajmg.a.62530
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Familial Cardiomyopathy Registry
中科院分区：
文献类型：
--
作者：
Gao S;Mumme-Monheit A;Chen SN;Spector EB;Slavov D;Baralle FE;Bristow MR;Mestroni L;Taylor MRG;Familial Cardiomyopathy Registry
扩张型心肌病（DCM）是由核纤层蛋白A/C（LMNA）基因突变引起的人类最常见的心脏表型之一。在我们的研究中，对57例因扩张型心肌病接受心脏移植的患者进行了LMNA变异筛查。我们在一个DCM家系中发现了LMNA外显子5最后一个核苷酸的同义变异c.936G>A。临床上，LMNA变异携带者表现为严重的家族性DCM、传导疾病和高肌酸激酶水平。LMNA c.936G>A变异体是新的，在目前的遗传变异体数据库中尚未报道。桑格测序结果显示，LMNA c.936 G>A变异体存在于基因组DNA中，但不存在于来自一个家族成员心脏组织的cDNA中。实时定量PCR（qPCR）显示，与对照相比，患者心脏中的LMNA mRNA水平显著降低，表明c.936G>A LMNA变体导致LMNA的mRNA降低和可能的蛋白质表达降低。这些发现扩大了对LMNA同义变异与DCM患者分子发病机制之间关系的理解。
Dilated cardiomyopathy (DCM) is one of the most common cardiac phenotypes caused by mutations of lamin A/C (LMNA) gene in humans. In our study, a cohort of 57 patients who underwent heart transplant for dilated cardiomyopathy was screened for variants in LMNA. We identified a synonymous variant c.936G>A in the last nucleotide of exon 5 of LMNA in a DCM family. Clinically, the LMNA variant carriers presented with severe familial DCM, conduction disease and high creatine-kinase level. The LMNA c.936G>A variant is novel and has not been reported in current genetic variant databases. Sanger sequencing results showed the presence of LMNA c.936G>A variant in the genomic DNA but not in the cDNA derived from one family member’s heart tissue. Real-time quantitative PCR (qPCR) showed significantly lower LMNA mRNA levels in the patient’s heart compared to the controls, suggesting that the c.936G>A LMNA variant resulted in reduced mRNA and possibly lower protein expression of LMNA. These findings expand the understanding on the association between synonymous variant of LMNA and the molecular pathogenesis in DCM patients.
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DOI：
10.1016/s0735-1097(02)01724-2
发表时间：
2002-03-20
影响因子：
24
作者：
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DOI：
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影响因子：
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