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

• Published in: Translational pediatrics Vol. 13; no. 3; pp. 484 - 491
• Main Authors: Lyu, Yongxue, Wang, Tao, Lin, Meifang, Qi, Fengfeng
• Format: Journal Article
• Language: English
• Published: China AME Publishing Company 27.03.2024
• Subjects: Case Report; neuropathological disorders; case report; Infantile neuroaxonal dystrophy (INAD); PLA2G6; c.1778C>T
• ISSN: 2224-4344; 2224-4336; 2224-4344
• DOI: 10.21037/tp-23-568

Infantile neuroaxonal dystrophy (INAD) is an ultra-rare early-onset autosomal recessive neurodegenerative disorder due to variants. The clinical symptoms of INAD patients display considerable diversity, and many variants are still not thoroughly investigated in relation to their associated clinical presentations. 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 gene. In the patient's asymptomatic parents and brother, the c.1778C>T variant stayed in heterozygous status as confirmed by Sanger sequencing. The patient was finally diagnosed with INAD. We report an INAD child with a rare c.1778C>T homozygous missense variant and associated clinical symptoms. The family-based cosegregation analysis reveals that the c.1778C>T homozygous variant contributes to the pathogenesis of INAD.