@article {442, title = {Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders.}, journal = {Genome Med}, volume = {9}, year = {2017}, month = {2017 08 14}, pages = {73}, abstract = {

BACKGROUND: De novo missense variants in CDK13 have been described as the cause of syndromic congenital heart defects in seven individuals ascertained from a large congenital cardiovascular malformations cohort. We aimed to further define the phenotypic and molecular spectrum of this newly described disorder.

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.

}, keywords = {Adolescent, Adult, CDC2 Protein Kinase, Child, Child, Preschool, Face, Female, Heart Defects, Congenital, Humans, Infant, Intellectual Disability, Male, Mutation, Phenotype, Syndrome}, issn = {1756-994X}, doi = {10.1186/s13073-017-0463-8}, author = {Bostwick, Bret L and McLean, Scott and Posey, Jennifer E and Streff, Haley E and Gripp, Karen W and Blesson, Alyssa and Powell-Hamilton, Nina and Tusi, Jessica and Stevenson, David A and Farrelly, Ellyn and Hudgins, Louanne and Yang, Yaping and Xia, Fan and Wang, Xia and Liu, Pengfei and Walkiewicz, Magdalena and McGuire, Marianne and Grange, Dorothy K and Andrews, Marisa V and Hummel, Marybeth and Madan-Khetarpal, Suneeta and Infante, Elena and Coban-Akdemir, Zeynep and Miszalski-Jamka, Karol and Jefferies, John L and Rosenfeld, Jill A and Emrick, Lisa and Nugent, Kimberly M and Lupski, James R and Belmont, John W and Lee, Brendan and Lalani, Seema R} }