A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation.

Abstract

Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting females. It is mainly caused by loss-of-function mutations that affect the coding sequence of exon 3 or 4 of methyl-CpG-binding protein 2 (MECP2). Severe neonatal encephalopathy resulting in death before the age of 2 years is the most common phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in females, and only one case of a male patient with MECP2-related severe neonatal encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is the first reported case of a male with classic RTT caused by a 5-bp duplication in the open-reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform, which has been reported in one female patient with classic RTT. Therefore, both males and females displaying at least some type of MeCP2_e1 mutation may exhibit the classic RTT phenotype.

• Authors: Narumi Tokaji, Hiromichi Ito, Tomohiro Kohmoto, Takuya Naruto, Rizu Takahashi, Aya Goji, Tatsuo Mori, Yoshihiro Toda, Masako Saito, Shoichiro Tange, Kiyoshi Masuda, Shoji Kagami, Issei Imoto
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 176 Issue 3 Pg. 699-702 (03 2018) ISSN: 1552-4833 [Electronic] United States
• PMID: 29341476 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• MECP2 protein, human
• Methyl-CpG-Binding Protein 2

Topics

• Alternative Splicing
• Base Sequence
• Brain (abnormalities)
• Child, Preschool
• DNA Mutational Analysis
• Exons
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Magnetic Resonance Imaging
• Male
• Methyl-CpG-Binding Protein 2 (genetics)
• Mutation
• Phenotype
• Rett Syndrome (diagnosis, genetics)