Prospective and detailed behavioral phenotyping in DDX3X syndrome

作者：Lara Tang, Tess Levy, Sylvia Guillory, Danielle Halpern, Jessica Zweifach, Ivy Giserman‐Kiss, Jennifer H. Foss‐Feig, Yitzchak Frank, Reymundo Lozano, Puneet Belani, Christina Layton, Bonnie Lerman, Emanuel Frowner, Michael S. Breen, Silvia De Rubeis, Ana Kostić, Alexander Kolevzon, Joseph D. Buxbaum, Paige M. Siper, Dorothy E. Grice · 发表于：Molecular Autism · 年份：2021 · DOI：10.1186/s13229-021-00431-z · 被引用次数：63 · 研究领域：Genomics and Rare Diseases、Congenital heart defects research、Genetics and Neurodevelopmental Disorders

BACKGROUND: DDX3X syndrome is a recently identified genetic disorder that accounts for 1-3% of cases of unexplained developmental delay and/or intellectual disability (ID) in females, and is associated with motor and language delays, and autism spectrum disorder (ASD). To date, the published phenotypic characterization of this syndrome has primarily relied on medical record review; in addition, the behavioral dimensions of the syndrome have not been fully explored. METHODS: We carried out multi-day, prospective, detailed phenotyping of DDX3X syndrome in 14 females and 1 male, focusing on behavioral, psychological, and neurological measures. Three participants in this cohort were previously reported with limited phenotype information and were re-evaluated for this study. We compared results against population norms and contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense variants or in-frame deletions. RESULTS: Eighty percent (80%) of individuals met criteria for ID, 60% for ASD and 53% for attention-deficit/hyperactivity disorder (ADHD). Motor and language delays were common as were sensory processing abnormalities. The cohort included 5 missense, 3 intronic/splice-site, 2 nonsense, 2 frameshift, 2 in-frame deletions, and one initiation codon variant. Genotype-phenotype correlations indicated that, on average, missense variants/in-frame deletions were associated with more severe language, motor, and adaptive deficits in co...