Two males with sick sinus syndrome in a family with 0.6 kb deletions involving major domains in MECP2

Takehiko Inui, Kazuhiro Iwama, Takuya Miyabayashi, Ryo Sato, Yukimune Okubo, Wakaba Endo, Noriko Togashi, Yosuke Kakisaka, Atsuo Kikuchi, Takeshi Mizuguchi, Shigeo Kure, Naomichi Matsumoto, Kazuhiro Haginoya

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in methyl-CpG-binding protein 2 (MECP2) in males can lead to various phenotypes, ranging from neonatal encephalopathy to intellectual disability. In this study, using Nord's method of next-generation sequencing in three siblings, we identified a 0.6 kb deletion involving the transcriptional repression domain (TRD). Two males and one female had intellectual disability and apnea, but none met the criteria of Rett syndrome. Both males had sick sinus syndrome and severe tracheomalacia that resulted in early death. The mother, with skewed X-inactivation, had no symptoms. Therefore, this mutation is pathological for both males and females, resulting in sick sinus syndrome and severe tracheomalacia with strong reproducibility in males. Deletions involving major domains in MECP2 can result in a severe phenotype, and deletion of the TRD domain can cause severe autonomic nervous system dysregulation in males in these cases.

Original languageEnglish
Article number103769
JournalEuropean Journal of Medical Genetics
Volume63
Issue number3
DOIs
Publication statusPublished - 2020 Mar

Keywords

  • Autonomic nervous system dysregulation
  • Large deletion
  • MECP2
  • Nord's method
  • Sick sinus syndrome
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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