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Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disease. Both TIEG1 (encoded by KLF10) knockout mice develop HCM with marked up-regulation of PTTG1, suggesting a loss-of-function mechanism in human disease ([PMID:22234868]). In a study of 923 unrelated, genotype-negative HCM patients, six novel heterozygous KLF10 missense variants were identified in six probands ([PMID:22234868]). One representative variant is c.80T>C (p.Met27Thr). No segregation data were reported. Functional assays demonstrated that five of the six TIEG1 mutants significantly increased PTTG1 promoter activity in luciferase reporter studies and yielded elevated PTTG1 protein expression by immunohistochemistry in diseased cardiac tissue, mirroring the phenotype of KLF10-deficient mice ([PMID:22234868]).
Gene–Disease AssociationLimitedSix unrelated probands with novel KLF10 missense variants ([PMID:22234868]); supportive functional data Genetic EvidenceLimitedSix novel heterozygous missense variants in six probands; no segregation reported Functional EvidenceModerateKLF10-knockout mice recapitulate HCM; luciferase promoter assays and cardiac IHC confirm increased PTTG1 expression ([PMID:22234868]) |