PLA2G6 gene mutation and infantile neuroaxonal degeneration; report of three cases from Iran

Infantile neuroaxonal degeneration (INAD) is a rare subgroup of neurodegeneration with brain iron accumulation (NBIA) disorders. This progressive disorder may develop during the early years of life. Affected individuals mostly manifest developmental delay and/or psychomotor regression as well as other neurological deficits. In the present study, we discussed 3 INAD patients diagnosed before the age of 10 by using Whole-Exome Sequencing (WES). We evaluated 3 pediatric patients with clinical phenotypes of INAD who underwent WES. Sanger sequencing was performed for co-segregation analysis of the variants in the families. An study was conducted for identification of the molecular function of the identified genetic variants in the gene. We detected three novel genetic variants in the PLA2G6 gene including a homozygous missense (NM_003560.2; c.1949T>C; p.Phe650Ser), a splicing (NM_001349864; c.1266-1G>A) and a frameshift variant (NM_003560.4; c.1547_1548dupCG; p.Gly517ArgfsTer29). Since the variants were not previously reported in literature or population databases, we performed in-silico studies for these variants and demonstrated their potential pathogenicity. The current study reports novel genetic variants in the gene in the Iranian population, emphasizing the importance of high-throughput genetic testing in rare diseases.