Novel insertion mutation in the PLA2G6 gene in an Iranian family with infantile neuroaxonal dystrophy

Abstract

Background: Infantile neuroaxonal dystrophy is an autosomal recessive neurological disorder. Individuals with infantile neuroaxonal dystrophy experience progressive loss of vision, mental skills and muscular control, and other variable clinical signs. Pathogenic variants in the PLA2G6 gene, encoding phospholipase A2, are recognized to be the fundamental reason for infantile neuroaxonal dystrophy. This study aimed to detect pathogenic variant in a consanguine Iranian family with infantile neuroaxonal dystrophy. Methods: The mutation screening was done by whole exome sequencing followed by direct Sanger sequencing. Results: We identified a homozygous insertion mutation, NM_003560: c.1548_1549insCG (p.G517Rfs*29) in exon 10 of PLA2G6 in the patient. The parents were heterozygous for variant. Conclusions: Because of the clinical heterogeneity and rarity of infantile neuroaxonal dystrophy, whole exome sequencing is critical to confirm the diagnosis and is an excellent tool for INAD management.

A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report

“…This phenomenon is likely attributed to the fact that INAD-related PLA2G6 variants result in more severe impairment of iPLA2-β enzymatic activity compared to PLA2G6 variants linked to other PLAN disorders ( 16 ). It is also noteworthy that the same PLA2G6 variant can lead to different clinical phenotypes among individuals ( 8 , 9 , 17 , 18 ). For example, compared to our INAD proband, patient (43-year-old man) with the PLA2G6 c.991G>T homozygous variant, which causes a 70% reduction in enzyme activity of iPLA2-β, developed AREP phenotypes with relatively later onset ages and slower disease progression ( 17 ).…”