A novel phenotype with splicing mutation identified in a Chinese family with desminopathy.
10.1097/CM9.0000000000000001
- Author:
Peng FAN
1
;
Chao-Xia LU
2
;
Xue-Qi DONG
3
;
Di ZHU
3
;
Kun-Qi YANG
1
;
Ke-Qiang LIU
2
;
Di ZHANG
3
;
Ying ZHANG
1
;
Xu MENG
1
;
Hui-Qiong TAN
3
;
Li-Tian YU
3
;
Ke-Fei DOU
1
;
Ya-Xin LIU
3
;
Xue ZHANG
2
;
Xian-Liang ZHOU
1
Author Information
1. Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
2. McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
3. Emergency and Critical Care Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Asian Continental Ancestry Group;
Cardiomyopathies;
genetics;
pathology;
Desmin;
genetics;
Electrocardiography;
Female;
Genotype;
Humans;
Male;
Middle Aged;
Muscular Dystrophies;
genetics;
pathology;
Mutation;
genetics;
Pedigree;
Phenotype
- From:
Chinese Medical Journal
2019;132(2):127-134
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy.
METHODS:Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy.
RESULTS:A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.
CONCLUSIONS:We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.
