Nicholas GOEL, Charles B. HUDDLESTON, Andrew C. FIORE

A novel mutation of the MYH7 gene in a patient with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized byasymmetric cardiac hypertrophy due to inherited mutations in genes thatencode sarcomeric proteins. MYH7, which encodes β-myosin heavy chain,is among the most commonly mutated genes in patients affected by HCM.We aimed to identify the specific mutation responsible for HCM in a sixmonth old Caucasian patient. NextGen DNA sequencing revealed a novelp.Ala1328Thr (A1328T) mutation of MYH7 in the affected patient as wellas his asymptomatic father and asymptomatic brother. The clinical detailsof this mutation are described for the first time in this report. The geneticvariant affects a residue that is highly conserved across species. Theoreticalanalysis suggests that A1328T is very likely deleterious to β-myosin heavychain protein structure and function. Furthermore, this novel mutation wasnot observed with any significant frequency in approximately 6,500 healthyindividuals of European and African American ancestry in the NHLBI ExomeSequencing Project, underlining the potential pathogenicity of this variant.

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