Spatiotemporal expression specificity analysis of Duchenne/Becker muscular dystrophy caused by DMD gene c.2622+2T＞C variant
10.16557/j.cnki.1000-7547.2024.02.003
- VernacularTitle:DMD基因c.2622+2T＞C导致假肥大型肌营养不良的时空表达特异性分析
- Author:
Liyu ZHANG
1
;
Fengyu CHE
;
Guoxia WANG
;
Benchang LI
;
Lidangzhi MO
;
Ying YANG
Author Information
1. 西安市儿童医院,陕西省儿科疾病研究所,西安 710003
- Keywords:
dystrophin gene;
splicing variation;
mini-gene technique;
Duchenne/Becker muscular dystrophy
- From:
Chinese Journal of Neuroanatomy
2024;40(2):153-161
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the gene variants of a patient affected with Duchenne/Becker muscular dystrophy in a pedigree and further explore the genotype-phenotype correlation for providing basis for family genetic counseling.Methods:The clinical features and family history of family members were collected.Multiplex ligation-dependent probe amplification(MLPA)was utilized to detect copy number variation of target genes.The pathogenic variations were ana-lyzed by whole exome sequencing(WES).The suspected gene variations were verified by Sanger sequencing.For the splice site mutations,mini-gene was constructed and expressed in vitro to detect the number of transcript and cDNA se-quence.Results:The proband of this family is a male,with no obvious involvement of the lower limbs.Laboratory tests showed an elevated level of creatine kinase(CK)in peripheral blood(700-1600 U/L),and electromyography showed myogenic damage.MLPA did not detect pathogenic exon copy number variation in dystrophin(DMD)gene.Genetic testing showed the proband carried a maternal hemizygotic splicing variation of DMD gene(NM_004006.2):c.2622+2T＞C.An in vitro mini-gene splicing assay confirmed that this splicing mutation could affect RNA splicing.According to clinical features and genetic testing results,the proband was speculated first proof of Duchenne/Becker muscular dys-trophy(DMD/BMD)caused by DMD gene mutation.Conclusion:This study identified the pathogenic variation of a proband with DMD/BMD of DMD gene,which enriched the variation spectrum of DMD/BMD in China.It was con-firmed that the splicing variation of the DMD gene c.2622+2T＞C can produce multiple transcripts leading to different functional impairments,and based on the specificity of temporal and spatial expression,it corresponded to the mild clin-ical manifestations of the patient,providing some reference value for the correlation between genotype and phenotype.
