title: A novel homozygous mutation of GJC2 derived from maternal uniparental disomy in a female patient with Pelizaeus-Merzbacher-like disease.
abstract: Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating disorder of the central nervous system characterized by nystagmus, motor developmental delay, ataxia, and progressive spasticity. The gap junction protein gamma-2 gene (GJC2), encoding the gap junction protein connexin 47, is one of the genes responsible for this condition. In this study, a novel homozygous mutation in GJC2 (c.746C>G; p.P249R) was identified in a 21-year-old female patient with PMLD. Although her mother was a carrier of this mutation, the Mendelian inheritance pattern could not be determined because the paternal sample was unavailable. Alternatively, chromosomal microarray testing together with single nucleotide polymorphism typing (CGH+SNP) was performed to determine the gene copy number and analyze the haplotype in the 1q42.13 region in which GJC2 is located. The result showed no deletion, but the GJC2 region was involved in the loss-of-heterozygosity region. Furthermore, haplotype of chromosome 1, in which GJC2 is located, revealed that both copies of chromosome 1 were derived from the patient's mother, indicating maternal uniparental disomy of chromosome 1. This study showed the advantage of the SNP genotyping microarray for detecting the origin of the mutation.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS), Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.forename: Ryuta
authors.initials: R
authors.lastname: Tanaka
authors.forename: Shino
authors.initials: S
authors.lastname: Shimada
authors.forename: Noriko
authors.initials: N
authors.lastname: Sangu
authors.forename: Junko
authors.initials: J
authors.lastname: Nakayama
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D002871:Chromosome Banding; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004827:Epilepsy / Q000453:epidemiology / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006239:Haplotypes; D006801:Humans; D017403:In Situ Hybridization; D007621:Karyotyping; D046228:Microarray Analysis; D009128:Muscle Spasticity / Q000209:etiology / Q000235:genetics; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009186:Myelin Sheath / Q000473:pathology; D009759:Nystagmus, Pathologic / Q000209:etiology / Q000235:genetics; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D024182:Uniparental Disomy / Q000235:genetics*; D055815:Young Adult
chemical_list: D017630:Connexins; C427305:connexin 47; D004247:DNA