Familial <scp>Bainbridge‐Ropers</scp> syndrome: Report of familial <scp><i>ASXL3</i></scp> inheritance and a milder phenotype
Schaida Schirwani, Emily Woods, David A. Koolen, Charlotte W. Ockeloen, Sally Ann Lynch, Karl Kavanagh, John M. Graham, Katheryn Grand, Tyler Mark Pierson, Jeffrey M. Chung, Meena Balasubramanian
Abstract
De novo truncating and splicing pathogenic variants in the Additional Sex Combs-Like 3 (ASXL3) gene are known to cause neurodevelopmental delay, intellectual disability, behavioral difficulties, hypotonia, feeding problems and characteristic facial features. We previously reported 45 patients with ASXL3-related disorder including three individuals with a familial variant. Here we report the detailed clinical and molecular characteristics of these three families with inherited ASXL3-related disorder. First, a father and son with c.2791_2792del p.Gln931fs pathogenic variant. The second, a mother, daughter and son with c.4534C > T, p.Gln1512Ter pathogenic variant. The third, a mother and her daughter with c.4441dup, p.Leu1481fs maternally inherited pathogenic variant. This report demonstrates intrafamilial phenotypic heterogeneity and confirms heritability of ASXL3-related disorder.