Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bostwick Bret L, McLean Scott, Posey Jennifer E, Streff Haley E, Gripp Karen W, Blesson Alyssa, Powell-Hamilton Nina, Tusi Jessica, Stevenson David A, Farrelly Ellyn, Hudgins Louanne, Yang Yaping, Xia Fan, Wang Xia, Liu Pengfei, Walkiewicz Magdalena, McGuire Marianne, Grange Dorothy K, Andrews Marisa V, Hummel Marybeth, Madan-Khetarpal Suneeta, Infante Elena, Coban-Akdemir Zeynep, Miszalski-Jamka Karol, Jefferies John L, Members of the Undiagnosed Diseases Network, Rosenfeld Jill A, Emrick Lisa, Nugent Kimberly M, Lupski James R, Belmont John W, Lee Brendan, Lalani Seema R
Аннотация
METHODS: To minimise ascertainment bias, we recruited nine additional individuals with CDK13 pathogenic variants from clinical and research exome laboratory sequencing cohorts. Each individual underwent dysmorphology exam and comprehensive medical history review.
RESULTS: We demonstrate greater than expected phenotypic heterogeneity, including 33% (3/9) of individuals without structural heart disease on echocardiogram. There was a high penetrance for a unique constellation of facial dysmorphism and global developmental delay, as well as less frequently seen renal and sacral anomalies. Two individuals had novel CDK13 variants (p.Asn842Asp, p.Lys734Glu), while the remaining seven unrelated individuals had a recurrent, previously published p.Asn842Ser variant. Summary of all variants published to date demonstrates apparent restriction of pathogenic variants to the protein kinase domain with clustering in the ATP and magnesium binding sites.
CONCLUSIONS: Here we provide detailed phenotypic and molecular characterisation of individuals with pathogenic variants in CDK13 and propose management guidelines based upon the estimated prevalence of anomalies identified.