The novel and recurrent variants in exon 31 of CREBBP in Japanese patients with Menke–Hennekam syndrome

Eriko Nishi, Toshiki Takenouchi, Fuyuki Miya, Tomoko Uehara, Kumiko Yanagi, Yuiko Hasegawa, Kimiko Ueda, Seiji Mizuno, Tadashi Kaname, Kenjiro Kosaki, Nobuhiko Okamoto

Research output: Contribution to journalArticlepeer-review

Abstract

Menke–Hennekam syndrome-1 (MKHK1) is a congenital disorder caused by the heterozygous variants in exon 30 or 31 of CREBBP (CREB binding protein) gene mapped on 16p13.3. It is characterized by psychomotor delay, variable impairment of intellectual disability (ID), feeding difficulty, autistic behavior, hearing impairment, short stature, microcephaly, and facial dysmorphisms. The CREBBP loss-of-function variants cause Rubinstein–Taybi syndrome-1 (RSTS1). The function of CREBBP leading to MKHK1 has not been clarified so far, and the phenotype of MKHK1 significantly differs from that of RSTS1. We examined six patients with de novo pathogenic variants affecting the last exon of CREBBP, and they shared the clinical features of MKHK1. This study revealed that one frameshift and three nonsense variants of CREBBP cause MKHK1, and inferred that the nonsense variants of the last exon could further help in the elucidation of the etiology of MKHK1.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part A
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • CREBBP
  • exon 31
  • Menke–Hennekam syndrome
  • Rubinstein–Taybi syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'The novel and recurrent variants in exon 31 of CREBBP in Japanese patients with Menke–Hennekam syndrome'. Together they form a unique fingerprint.

Cite this