MeCP2_e2 partially compensates for lack of MeCP2_e1: A male case of Rett syndrome.
Mol Genet Genomic Med
; 8(2): e1088, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31816669
ABSTRACT
BACKGROUND:
Rett syndrome (RTT) is a neurodevelopmental disorder that predominantly affects girls. Its causative gene is the X-linked MECP2 encoding the methyl-CpG-binding protein 2 (MeCP2). The gene comprises four exons and generates two isoforms, namely MECP2_e1 and MECP2_e2. However, it remains unclear whether both MeCP2 isoforms have similar function in the brain.METHODS:
We report a case of a boy with typical RTT. Male cases with MECP2 variants have been considered inviable, but somatic mosaicism of the variants can cause RTT in males. Whole-exome sequencing was performed to search for the genetic background.RESULTS:
A novel nonsense and mosaic variant was identified in exon 1 of MECP2, and the variant allele fraction (VAF) was 28%. Our patient had the same level of VAF as that in reported male cases with mosaic variants in MECP2 exon 3 or 4, but manifested RTT symptoms that were milder in severity compared to those in these patients.CONCLUSION:
This is probably because the variants in MECP2 exon 3 or 4 disrupt both isoforms of MeCP2, whereas the variant in exon 1, as presented in this study, disrupts only MeCP2_e1 but not MeCP2_e2. Therefore, our findings indicate that MeCP2_e2 may partially compensate for a deficiency in MeCP2_e1.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Síndrome de Rett
/
Proteína 2 de Unión a Metil-CpG
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Humans
/
Male
Idioma:
En
Año:
2020
Tipo del documento:
Article