Two novel gap junction protein alpha 12 gene mutations in two Chinese patients with Pelizaeus–Merzbacher-like disease

Abstract Pelizaeus–Merzbacher-like disease (PMLD) is a hypomyelinating disorder of the central nervous system caused by mutation in the gap junction protein alpha 12 ( GJA12 ) gene. Uniparental disomy (UPD) is defined as the presence of a chromosome pair, in a diploid individual, that derives from only one parent. Here, we analyzed GJA12 gene mutations in two Chinese PMLD patients and two novel mutations of GJA12 c.216delGinsAA (c.P73fsX106) caused by paternal UPD for chromosome 1 and c.138C>G (p.I46M) were identified. The patient 1 harbored a homozygous frameshift mutation at c.216delGinsAA (p.P73fsX106) in the GJA12 . Haplotype analysis of the entire chromosome 1 of the patient revealed that this chromosome was exclusively derived from her father. The GJA12 gene is located on chromosome 1q41-42 and falls within the region of paternal isodisomy on the q arm. Thus, a novel homozygous frameshift mutation p.P73fsX106, caused by paternal UPD for chromosome 1, was identified in patient 1 with PMLD. Patient 2 was found a homozygous missense mutation at c.138C>G (p.I46M). This is the first GJA12 gene mutations reported from two Chinese PMLD patients and one mutation was associated with UPD for chromosome 1.