De novo variants in CDK13 associated with syndromic ID/DD; molecular and clinical delineation of 15 individuals and a further review.

De novo variants in CDK13 associated with syndromic ID/DD; molecular and clinical delineation of 15 individuals and a further review.
Clin Genet. 2018 Feb 02;:
Authors: van den Akker WMR, Brummelman I, Martis LM, Timmermans RN, Pfundt R, Kleefstra T, Willemsen MH, Gerkes EH, Herkert JC, van Essen AJ, Rump P, Vansenne F, Terhal PA, van Haelst MM, Cristian I, Turner CE, Cho MT, Begtrup A, Willaert R, Fassi E, van Gassen KLI, Stegmann APA, de Vries BBA, Schuurs-Hoeijmakers JHM
Abstract
De novo variants in the gene encoding cyclin-dependent kinase 13 (CDK13) have been associated with congenital heart defects and intellectual disability (ID). Here, we present the clinical assessment of fifteen individuals and report novel de novo missense variants within the kinase domain of CDK13. Furthermore, we describe two nonsense variants and a recurrent frame-shift variant. We demonstrate the synthesis of two aberrant CDK13 transcripts in lymphoblastoid cells from an individual with a splice-site variant. Clinical characteristics of the individuals include mild to severe ID, developmental delay, behavioural problems, (neonatal) hypotonia and a variety of facial dysmorphism. Congenital heart defects were present in two individuals of the current cohort, but in at least 42% of all known individuals. An overview of all published cases is provided and does not demonstrate an obvious genotype-phenotype correlation, although two individuals harbouring a ...

Source: Clinical Genetics - February 2, 2018 Category: Genetics & Stem Cells Authors: van den Akker WMR, Brummelman I, Martis LM, Timmermans RN, Pfundt R, Kleefstra T, Willemsen MH, Gerkes EH, Herkert JC, van Essen AJ, Rump P, Vansenne F, Terhal PA, van Haelst MM, Cristian I, Turner CE, Cho MT, Begtrup A, Willaert R, Fassi E, van Gassen KL Tags: Clin Genet Source Type: research