BHLHA9 and Alzheimer disease: Copy number gains of BHLHA9 in humans have been described in association with the triplosensitivity trait (defined as a phenotype produced by an additional copy of the gene) potentially causing a gain-of-function (GoF) hypermorphic allele of SHFM with long bone deficiency (SHFLD3; MIM: 612576) as an AD trait with less than 50% penetrance and variable phenotypic expression.50, 51, 52 Family HOU3586 was referred from Brazil and has been published previously.53