Reevaluating the pathogenicity of the variations c.439 G>A and c.2132 C>T in the PLA2G6 gene

The phospholipase A2 group VI ( PLA2G6 ) gene encodes for a Ca 2+ -independent PLA 2 , which is localized in the cytosol, in the endoplasmic reticulum and in the mitochondrial membrane, plays a major role in phospholipid remodelling. Mutations within this gene have been reported to cause different phenotypes: infantile-onset neuroaxonal dystrophy associated with brain iron accumulation and adult-onset parkinsonian syndrome. In the present study, we analysed the PLA2G6 gene sequence in an asymptomatic young woman that was referred to our laboratory by a geneticist for an history of infantile neuroaxonal dystrophy in her little maternal cousin in whom the results of the genetical analysis were not available. We found two variants in the PLA2G6 gene (NM_003560.4, c.439 G>A and c.2132 C>T, p.Ala147Thr and p.Pro711Leu) previously reported as pathogenic. These results prompted us to perform a segregation analysis in the parents of this woman and we only found the presence of both variants in the asymptomatic 56-year-old patient’s mother. Our molecular genetic testing clearly indicates that the c.439 G>A and c.2132 C>T variations identified in the PLA2G6 gene are positioned in cis and are not responsible for infantile neuroaxonal dystrophy which is an autosomal recessive disease.