ORIGINAL ARTICLE   

Minerva Pediatrics 2023 February;75(1):32-8

DOI: 10.23736/S2724-5276.16.04451-0

Copyright © 2016 EDIZIONI MINERVA MEDICA

language: English

Identification of GJC2 gene mutations in Chinese patients with Pelizaeus-Merzbacher-like disease

Taoyun JI ¹, Dongxiao LI ¹, Ye WU ¹, Jiangxi XIAO ², Haoran JI ¹, Xiru WU ¹, Jingmin WANG ¹ ✉, Yuwu JIANG ¹

¹ Department of Pediatrics, Peking University First Hospital, Beijing, China; ² Department of Radiology, Peking University First Hospital, Beijing, China

BACKGROUND: Clinical and genetic features were analyzed in five pedigrees with Pelizaeus-Merzbacher-like disease (PMLD) to provide bases for genetic counseling and prenatal diagnosis.
METHODS: Clinical data including medical history, physical signs, and auxiliary examinations were collected from six patients and their family numbers in five pedigrees with PMLD. Polymerase chain reaction and sequence analysis were used to amplify GJC2 and PLP1 alterations, while multiplex ligation-dependent probe amplification (MLPA) was performed to detect PLP1 dosage changes. The gene mutations were diagnosed for further analysis of the genetic features.
RESULTS: A total of seven GJC2 mutations were identified in these patients, including two novel missense mutations (c.217C>T, p.Pro73Ser; c.1199C>A, p.Ala400Glu), one nonsense mutation (c.735C>A, p.Cys245X), three novel frameshift mutations (c.579delC, p.Gly193fsX17 and c.1296_1297insG, p.Gly433fsX59; c.689delG, p.Gly230AlafsX241), and one known missense mutation (c.814T>G, p.Tyr272Asp). Compound heterozygotes were found for P1-3, while homozygotes were found for P4-6 that were inherited from their parents with normal phenotypes except for P5 and P6, respectively. The c.814T>G (p.Tyr272Asp) mutation in P5 was de novo. A c.1199C>A (p.Ala400Glu) homozygous mutation in GJC2 was identified in P6. A heterozygous variation was found in his father and the wild type was seen in his mother.
CONCLUSIONS: Six patients from five pedigrees were diagnosed with PMLD based on their clinical data. Six GJC2 novel mutations were found in this study, expanding the spectrum of GJC2 mutations. This is the second group of GJC2 mutations reported from six Chinese patients with PMLD.

KEY WORDS: Pelizaeus-Merzbacher like brain sclerosis; Connexin 47; Mutation