Yan Ji1, Yusheng Li1, Changhe Shi1, Yuan Gao1, Jing Yang1, Dongyi Liang2, Zhihua Yang2, Yuming Xu3. 1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. 2. The Medical College of ZhengZhou University, Zhengzhou, Henan, 450050, China. 3. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: xuyuming@zzu.edu.cn.
Abstract
INTRODUCTION: This study reports a novel mutation site of the phospholipase A2 group VI (PLA2G6) gene, and analyzes the information of 67 previously published cases to elucidate PLA2G6 phenotype-genotype variations. METHODS: We collected clinical data and examined gene mutation sites from one Chinese patient with adult-onset ataxia and her family. Next-generation sequencing (NGS) and Sanger sequencing were used to verify possible mutations. PolyPhen-2, SIFT, and MutationTaster were used to predict their pathogenicity. For analyzing the distribution frequency of the mutation, 597 healthy controls were recruited. We also analyzed the clinical and genetic information of 67 cases from 23 studies in Pubmed database. RESULTS: A novel compound heterozygous mutation of the PLA2G6 gene, c.1648delC and c.991G > T, was found in the Chinese patient, and classified as pathogenic. The c.1648delC variation was absent in ExAC, 1000G, dbSNP databases and the 597 healthy controls. Of the 67 cases, 29 presented ataxia. The signs of cerebellar atrophy appeared in the MRIs of most patients, while signs of iron accumulation were absent in older-aged patients with a compound heterozygous mutation. Thirty-eight patients showed no ataxia. A negative or mild extrapyramidal symptom accompanied by a low age, a homogenous mutation, while moderate or severe extrapyramidal symptoms were associated with an old age and a compound heterozygous mutation. CONCLUSION: A novel compound heterozygous mutation of the PLA2G6 gene, c.1648delC and c.991G > T, is associated with adult onset ataxia. Phenotype-genotype variations of PLA2G6 are predicted to be caused by the loss of protein or enzyme activity of phospholipase-2.
INTRODUCTION: This study reports a novel mutation site of the phospholipase A2 group VI (PLA2G6) gene, and analyzes the information of 67 previously published cases to elucidate PLA2G6 phenotype-genotype variations. METHODS: We collected clinical data and examined gene mutation sites from one Chinese patient with adult-onset ataxia and her family. Next-generation sequencing (NGS) and Sanger sequencing were used to verify possible mutations. PolyPhen-2, SIFT, and MutationTaster were used to predict their pathogenicity. For analyzing the distribution frequency of the mutation, 597 healthy controls were recruited. We also analyzed the clinical and genetic information of 67 cases from 23 studies in Pubmed database. RESULTS: A novel compound heterozygous mutation of the PLA2G6 gene, c.1648delC and c.991G > T, was found in the Chinese patient, and classified as pathogenic. The c.1648delC variation was absent in ExAC, 1000G, dbSNP databases and the 597 healthy controls. Of the 67 cases, 29 presented ataxia. The signs of cerebellar atrophy appeared in the MRIs of most patients, while signs of iron accumulation were absent in older-aged patients with a compound heterozygous mutation. Thirty-eight patients showed no ataxia. A negative or mild extrapyramidal symptom accompanied by a low age, a homogenous mutation, while moderate or severe extrapyramidal symptoms were associated with an old age and a compound heterozygous mutation. CONCLUSION: A novel compound heterozygous mutation of the PLA2G6 gene, c.1648delC and c.991G > T, is associated with adult onset ataxia. Phenotype-genotype variations of PLA2G6 are predicted to be caused by the loss of protein or enzyme activity of phospholipase-2.
Authors: Yalan Wan; Yanyan Jiang; Zhiying Xie; Chen Ling; Kang Du; Ran Li; Yun Yuan; Zhaoxia Wang; Wei Sun; Haiqiang Jin Journal: Front Neurol Date: 2022-07-13 Impact factor: 4.086