PLA۲G۶ gene mutation and infantile neuroaxonal degeneration; report of three cases from Iran

Objective(s): 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 ۳ INAD patients diagnosed before the age of ۱۰ by using Whole-Exome Sequencing (WES).Materials and Methods: We evaluated ۳ 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 in-silico study was conducted for identification of the molecular function of the identified genetic variants in the PLA۲G۶ gene.Results: We detected three novel genetic variants in the PLA۲G۶ gene including a homozygous missense (NM_۰۰۳۵۶۰.۲; c.۱۹۴۹T>C; p.Phe۶۵۰Ser), a splicing (NM_۰۰۱۳۴۹۸۶۴; c.۱۲۶۶-۱G>A) and a frameshift variant (NM_۰۰۳۵۶۰.۴; c.۱۵۴۷_۱۵۴۸dupCG; p.Gly۵۱۷ArgfsTer۲۹). 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.Conclusion: The current study reports novel genetic variants in the PLA۲G۶ gene in the Iranian population, emphasizing the importance of high-throughput genetic testing in rare diseases.

کلیدواژه ها:

Developmental disabilities ، magnetic resonance imaging ، Neuroaxonal dystrophies ، Pantothenate kinase associated neuro degeneration ، Whole exome sequencing