Redefining the phenotypic spectrum of de novo heterozygous CDK13 variants: Three patients without cardiac defects

Tomoko Uehara, Toshiki Takenouchi, Rika Kosaki, Kenji Kurosawa, Seiji Mizuno, Kenjiro Kosaki

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2 Citations (Scopus)

Abstract

Recently, 7 patients with de novo constitutional non-synonymous mutations in the CDK13 gene were ascertained through a trio exome analysis of a large cohort of 610 patients with congenital cardiac diseases. Despite another report describing 9 additional patients, the clinical spectrum of this condition has yet to be defined. Herein, we report 3 patients with heterozygous constitutional CDK13 mutations, who were ascertained through exome analysis of children with intellectual disability and minor anomalies, who lacked cardiac anomalies. Two patients had a c.2149G > A, p.Gly717Arg mutation, and one had a c.2525A > G, p. Asn842Ser mutation. A review of the previously described patients and those described herein has enabled the following points to be clarified. First, congenital heart diseases are not an essential feature (13/19). Second, nasal features may help syndromic recognition (14/16). Third, widely spaced and peg-shaped teeth may represent a previously unappreciated diagnostic clue for this newly identified syndrome. Here, we show that p.Gly717Arg represents a hotspot in addition to p.Asn842Ser. We suggest that this CDK13-related disorder may represent a clinically recognizable syndrome.

Original languageEnglish
JournalEuropean Journal of Medical Genetics
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Exome
Mutation
Heart Diseases
Disabled Children
Nose
Intellectual Disability
Tooth
Genes

Keywords

  • CDK13
  • Congenital cardiac diseases
  • Intellectual disability
  • Widely spaced and peg-shaped teeth

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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abstract = "Recently, 7 patients with de novo constitutional non-synonymous mutations in the CDK13 gene were ascertained through a trio exome analysis of a large cohort of 610 patients with congenital cardiac diseases. Despite another report describing 9 additional patients, the clinical spectrum of this condition has yet to be defined. Herein, we report 3 patients with heterozygous constitutional CDK13 mutations, who were ascertained through exome analysis of children with intellectual disability and minor anomalies, who lacked cardiac anomalies. Two patients had a c.2149G > A, p.Gly717Arg mutation, and one had a c.2525A > G, p. Asn842Ser mutation. A review of the previously described patients and those described herein has enabled the following points to be clarified. First, congenital heart diseases are not an essential feature (13/19). Second, nasal features may help syndromic recognition (14/16). Third, widely spaced and peg-shaped teeth may represent a previously unappreciated diagnostic clue for this newly identified syndrome. Here, we show that p.Gly717Arg represents a hotspot in addition to p.Asn842Ser. We suggest that this CDK13-related disorder may represent a clinically recognizable syndrome.",
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AU - Mizuno, Seiji

AU - Kosaki, Kenjiro

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N2 - Recently, 7 patients with de novo constitutional non-synonymous mutations in the CDK13 gene were ascertained through a trio exome analysis of a large cohort of 610 patients with congenital cardiac diseases. Despite another report describing 9 additional patients, the clinical spectrum of this condition has yet to be defined. Herein, we report 3 patients with heterozygous constitutional CDK13 mutations, who were ascertained through exome analysis of children with intellectual disability and minor anomalies, who lacked cardiac anomalies. Two patients had a c.2149G > A, p.Gly717Arg mutation, and one had a c.2525A > G, p. Asn842Ser mutation. A review of the previously described patients and those described herein has enabled the following points to be clarified. First, congenital heart diseases are not an essential feature (13/19). Second, nasal features may help syndromic recognition (14/16). Third, widely spaced and peg-shaped teeth may represent a previously unappreciated diagnostic clue for this newly identified syndrome. Here, we show that p.Gly717Arg represents a hotspot in addition to p.Asn842Ser. We suggest that this CDK13-related disorder may represent a clinically recognizable syndrome.

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