Patients with hypertrophic cardiomyopathy (HC) caused by compound variants have severe
clinical manifestations, but significant clinical heterogeneity remains. Clinical
diversity in these patients may result from different combinations of variants. We
analyzed the role of cis-compound variants in a Chinese HC pedigree. Exome sequencing was performed in the
proband. Identified variants were detected with bi-directional Sanger sequencing in
a pedigree that comprised 3 generations and 28 family members. Follow-up was performed
for 16 years. Two missense variants (c.2465T>C, p.Met822Thr; c.4258C>T, p.Arg1420Trp)
were identified in the MYH7 gene. These variants were absent in our 761 in-house people without HC and predicted
to be pathogenic.Both variants were detected in 11 family members, thus they were
believed to inherit cis. In the 11 members, only 5 developed HC, the other 6 were asymptomatic variant carriers
with an abnormal electrocardiogram. The HC members had mild hypertrophy with a maximum
left ventricular wall thickness of 13 to 21 mm and showed a low incidence of cardiovascular
events. In conclusion, the cis-compound variants of Met822Thr and Arg1420Trp in MYH7 are causal but relatively benign, variants associated with familial HC. This finding
suggests that different types of compound variants might need to be analyzed for a
genotype–phenotype study.
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Article Info
Publication History
Published online: January 20, 2022
Received in revised form:
November 17,
2021
Received:
September 7,
2021
Footnotes
Yubao Zou, Jizheng Wang, and Lei Song are joint corresponding authors.
Funding: This work was supported by grants CAMS-I2M, 2016-I2M-1-015 from CAMS Innovation Fund for Medical Sciences and grant No.: 81870286 and 81670274 from National Natural Science Foundation of China.
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