The GJA12/GJC2 (GJA12 was recently renamed GJC2) encodes the gap junction protein connexin47 (Cx47), which is a member of the connexin family of highly conserved integral membrane proteins. This gene is highly expressed in oligodendrocytes; it plays a key role in central myelination and is involved in peripheral myelination in humans. In addition, Gap channels are specialized cell-cell contacts that allow passive diffusion of molecules up to 1 kDa, including nutrients, metabolites (glucose), ions (K+, Ca2+) and second messengers (IP3, cAMP).
Defects in this protein are the cause of leukodystrophy, hypomyelinating, 2 (HLD2), lymphedema, hereditary, 1C (LMPH1C), and spastic paraplegia 44, autosomal recessive (SPG44).
The GJC2 gene, previously named as GJA12, was mapped on chromosome 1 (1q42.13). It spans approximately 10 kb in the genomic DNA with one coding exon. The GJC2 sequence encodes the 436-amino-acid gap junction connexin protein, Cx47. It comprises four transmembrane, two extracellular, and three cytoplasmic domains.
To date, 25 different GJC2 mutant alleles including nine missense, ten frameshift, three nonsense, one microinsertion and one regulatory mutations have been reported in PMLD1 patients. In addition, a GJC2 missense mutation causing a milder phenotype, the spastic paraplegia autosomal recessive type 44 has been reported.
Bugiani et al. (2006) performed GJA12 genetic analysis for 13 patients with Pelizaeus-Merzbacher-Like Disease (PMLD) from 10 families. Eight of the patients (patients 5 to 12) were from multi-consanguineous Saudi family. A 22-bp duplication mutation starting at nucleotide 371 was found in these eight PMLD patients. This mutation causes a frameshift, leading to a prematurely truncated Cx47 protein.