RGD Reference Report - Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders. - Rat Genome Database

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Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders.

Authors: 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 
Citation: Bostwick BL, etal., Genome Med. 2017 Aug 14;9(1):73. doi: 10.1186/s13073-017-0463-8.
RGD ID: 155631312
Pubmed: PMID:28807008   (View Abstract at PubMed)
PMCID: PMC5557075   (View Article at PubMed Central)
DOI: DOI:10.1186/s13073-017-0463-8   (Journal Full-text)


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.

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Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormal ear morphology  IAGP 155631312DNA:Mutations:cds :RGD 
Abnormal heart morphology  IAGP 155631312DNA:Mutations:cds :RGD 
Delayed gross motor development  IAGP 155631312DNA:Mutations:cds :RGD 
Delayed speech and language development  IAGP 155631312DNA:Mutations:cds :RGD 
Epicanthus  IAGP 155631312DNA:Mutations:cds :RGD 
Global developmental delay  IAGP 155631312DNA:Mutations:cds :RGD 
Hypertelorism  IAGP 155631312DNA:Mutations:cds :RGD 
Morphological central nervous system abnormality  IAGP 155631312DNA:Mutations:cds :RGD 
Short columella  IAGP 155631312DNA:Mutations:cds :RGD 
Thin upper lip vermilion  IAGP 155631312DNA:Mutations:cds :RGD 
Wide nasal bridge  IAGP 155631312DNA:Mutations:cds :RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cdk13  (cyclin-dependent kinase 13)

Genes (Mus musculus)
Cdk13  (cyclin dependent kinase 13)

Genes (Homo sapiens)
CDK13  (cyclin dependent kinase 13)


Additional Information