关键词: β-心肌肌肉球蛋白重链7基因, 新发突变, 临床特征, 扩张型心肌病1S型

Abstract:

Objective Whole exome sequencing has been used to analyze the variation in one child with left cardiac system dilation，perform pedigree analysis and confirm the etiology of dilated cardiomyopathy type 1S(DCMIS). Methods The clinical data of this child were collected. Chromosome copy number variation sequencing(CNV-seq) was used to determine deletions and duplications in chromosome structure. Whole exome sequencing was also used to analyze the variation in the child，and the variation sites were verified by Sanger sequencing in the child and parents，fraternal sister. The hazard of variation sites was assessed through bioinformatics analysis. Results Color Doppler ultrasound showed decreased left cardiac function，significant dilation and enlargement of left cardiac system，pulmonary hypertension，mitral regurgitation and tricuspid regurgitation. CNV-seq results showed seq[hg19]46，XN，and no chromosome abnormalities were found. Whole exome sequencing showed heterozygous variation in the beta-myosin heavy chain 7(MYH7) gene [c.1574A>G(p.Glu525Gly)]. No relevant reports were found in the OMIM and ClinVar databases. In the ESP database，1000 Genomes database，ExAC database and gnomAD database，the variation site was not included and was a new variation. Sanger sequencing confirmed the existence of variation，and the MYH7 gene of the parents and sister was normal. The MYH7 c.1574A>G(p.Glu525Gly) resulted in the loss of the hydrogen bond side chain interaction between protein side chain O atom and lysine side chain N atom at position 484. Conclusions The c.1574A>G(p.Glu525Gly)，a newly discovered variation of MYH7 gene，is responsible for the significant expansion of left cardiac system. The determination of new variation has enriched the understanding of DCMIS pathogenesis.

Key words: Beta-myosin heavy chain 7, New variation, Clinical characteristic, Dilated cardiomyopathy type 1S