重複遺伝子変異を伴った家族性肥大型心筋症家系における表現型の多様性

概要

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Although mutations of sarcomere protein genes and mitochondorial DNA (mtDNA) cause familial hypertrophic cardiomyopathy (FHC), the phenotypic expression varies in patients who harbor not only a different disease gene mutation, but also the same one. To investigate phenotypic variability in FHC patients, we analyzed the clinical findings, and performed mutation analysis of the cardiac β-myosin heavy chain (β-MHC) gene, the cardiac troponin T (Tn-T) gene and mtDNA in patients of two FHC families. In all five patients of family A, we found the β-MHC gene mutation (Gly741Trp) and mtDNA mutation (T3394C). In four patients of family B, in addition to the β-MHC gene mutation (Gly741Trp) which we reported previously, the rare polymorphic Tn-T gene mutation (Lys253Arg) was detected in an affected son and unaffected father. Also, nine polymorphic mtDNA missense mutations were found in the affected son and an affected daughter. Especially, six out of nine mutations were found to locate at evolutionarily conservative regions. Coexistence of other genetic abnormalities in β-MHC linked FHC, such as multiple polymorphic mtDNA mutations, may contribute to varying phenotypic expression and explain the heterogeneous behavior of FHC.
東京女子医科大学の論文
2001-10-25