Infantile neuroaxonal dystrophy caused by PLA2G6 gene mutation in a Chinese patient: A case report

Abstract

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disorder. Phospholipase A2 group VI (PLA2G6) gene mutations have been identified in the majority of individuals with INAD. The present case report is on a Chinese female pediatric patient (age, 18 months) diagnosed with INAD with deafness. To date, only four cases of INAD with hearing loss have been reported, PLA2G6-association has not been investigated. Next-generation DNA sequencing technology was used to identify disease-associated genes and Sanger sequencing was applied to verify the mutation in the patient's pedigree. Two mutations were identified in the PLA2G6 gene: c.1T>C (E2) and c.497 (E4) to c.496 (E4): Insert C. The distribution frequency of those mutations in the Single Nucleotide Polymorphism, HapMap, 1000 Genomes and Exome Aggregation Consortium databases was 0. However, cases of INAD appear to be underreported, particularly those from China. The identification of two mutations in the present study suggests unique PLA2G6 mutations in Chinese patients, and greatly expands on the spectrum of known mutations in INAD patients.

PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes

“…Individuals carrying the PLA2G6 mutation can also have different clinical phenotypes depending on specific genotypic features. The previous reported mutation sites of PLA2G6 are listed in Figure 1 (1, 2, 6–8, 13, 15–18, 22, 23, 30, 34, 38, 41–43, 45, 47, 51–69). Reportedly, in two PLA2G6 mutation families, all three patients carried PLA2G6 mutations (p.R632W) but presented different clinical manifestations than previously reported (13, 43).…”

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

“…To date, various mutations particularly missense variants or deletions have been reported from the PLA2G6 gene associated with the disease. 7 , 8 , 9 , 11 , 14 , 15 , 16 , 17 So far, insertion mutations have not been described for this gene. However, this type of mutations can lead to loss of function by disrupting the reading frame, of course, is consistent with the autosomal recessive inheritance pattern.…”

“…4 Homozygote mutations in the PLA2G6 gene have been recognized as the most common cause of INAD. 3,[7][8][9] The PLA2G6 gene is located on of the chromosome 22q13.1 and contains of 17 exons.…”

“…Homozygote mutations in the PLA2G6 gene have been recognized as the most common cause of INAD. 3 , 7 , 8 , 9 The PLA2G6 gene is located on of the chromosome 22q13.1 and contains of 17 exons. The protein encoded by this gene called a phospholipase A2 (Group VI) that involved the release of fatty acids from phospholipids.…”

Audiological Findings in Children with PLA2G6-Associated Neurodegeneration

“…While the clinical phenotype of children with INAD due to PLAN has been reported in detail, there are only limited reports on the audiological manifestations. Most reports include only sparse description and classify the hearing impairment as a 'sensorineural hearing loss' without a clear description of its characteristics [6][7][8][9][10] . In this study we sought to analyze the audiological manifestations in children with INAD.…”