Objective To investigate the pathogenic characteristics in PLA2G6 gene mutation of infantile neuroaxonal dystrophy(INAD),enrich the gene mutation spectrum of INAD,and provide a theoretical basis for INAD-related genetic counseling.Methods Clinical data related to the family of a proband were collected.Whole exome sequencing followed by Sanger sequencing was performed for the proband and her parents to screen for possible pathogenic mutation sites.The mutation sites were verified by Sanger sequencing,and the pathogenicity of the mutation sites was predicted by combining bioinformatics analysis.Finally,prenatal diagnosis was provided for the pregnant woman through amniocentesis.Results Whole exome sequencing results showed that the proband with clinical manifestations of psychomotor development regression was compound heterozygous mutations in the PLA2G6 gene c.1A＞G(p.M1?)and c.2242G＞A(p.A748T),with her father being a carrier of c.1A＞G(p.M1?)heterozygous mutation,and her mother a carrier of c.2242G＞A(p.A748T)heterozygous mutation.According to the American College of Medical Genetics and Genomics guidelines for variant rating,c.1A＞G(p.M1?)was a pathogenic mutation,while c.2242G＞A(p.A748T)was a variant of uncertain significance.Prenatal diagnosis showed that the fetus was a carrier of the c.1A＞G(p.M1?)heterozygous mutation.The pregnant woman later gave birth to a live boy at full term,and the baby had normal growth and development during the follow-up of 7 months after delivery.Conclusion The compound heterozygous mutations c.1A＞G(p.M1?)and c.2242G＞A(p.A748T)in PLA2G6 gene are the pathogenic mutations of the proband with INAD,of which c.2242G＞A(p.A748T)is a newly identified mutational site,which expands the genetic mutation map of INAD,and the whole exome sequencing data provide accurate genetic counseling and prenatal diagnosis for this family.
维普
万方数据