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

Abstract

Background: Infantile neuroaxonal dystrophy (INAD) is an ultra-rare early-onset autosomal recessive neurodegenerative disorder due to PLA2G6 variants. The clinical symptoms of INAD patients display considerable diversity, and many PLA2G6 variants are still not thoroughly investigated in relation to their associated clinical presentations. Case Description: A 16-month-old boy was admitted to our hospital due to regression of acquired motor and speech abilities that had persisted for 4 months. The patient was born to a healthy consanguineous couple after 41 weeks of pregnancy and natural delivery. Before 12 months old, he had normal motor development milestones. On admission, he also showed astasia-abasia, weakness of distal muscles, and diminished patellar tendon reflex. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy. Auditory brainstem response (ABR) indicated moderately severe hearing loss. With chromosome microarray analysis (CMA), we identified several copy number-neutral regions of runs of homozygosity (ROH) in the patient. Whole-exome sequencing (WES) further revealed that the patient harbored a homozygous missense variant NM_003560.2: c.1778C>T, p.Pro593Leu (rs1451486649) in the PLA2G6 gene. In the patient's asymptomatic parents and brother, the PLA2G6 c.1778C>T variant stayed in heterozygous status as confirmed by Sanger sequencing. The patient was finally diagnosed with INAD. Conclusions: We report an INAD child with a rare PLA2G6 c.1778C>T homozygous missense variant and associated clinical symptoms. The family-based cosegregation analysis reveals that the PLA2G6 c.1778C>T homozygous variant contributes to the pathogenesis of INAD.