Follow-Up Study and Genetic Analysis of Chinese Patients with Infantile Neuroaxonal Dystrophy

Objective Phenotype and genotype of 26 Chinese patients were analyzed in this study,which is helpful for the molecular diagnosis and genetic counseling in China.Methods Clinical diagnosis of infantile neuroaxonal dystrophy(INAD) was based on the criteria proposed.Patients were followed up from 10 months to 8 years since their first visit to evaluate the progression of motor and cognitive functions.Motor function was classified on Chinese version of Gross Motor Function Classification System(GMFCS).Mutations and copy number variations in PLA2G6 were detected by DNA sequencing and high-density oligonucleotide-microarray-based comparative genomic Hybridization(aCGH),respectively.Results Twenty-six patients were clinically diagnosed from Sep.2003 to Aug.2011.1.Clinical features were that almost all individuals were free of symptoms at birth and achieved normal developmental milestones before disease onset.The average age at onset was 1 year and 3 months.All patients presented with rapid motor and cognitive regression.Severe motor function impairments were shown in most patients at their first visit,with the average disease course 1.41 years.GMFCS Ⅴ was found in 11 cases,GMFCS Ⅳ in 12 cases,GMFCS Ⅲ in 1 case,and GMFCS Ⅱ in 2 cases.Babinski signs in physical examination,cerebellar atrophy shown in brain MRI and denervation in the electromyography were found in most of the patients.Twenty-three patients were followed up,with the average disease course 3.88 years,2 boys died from infection.The remaining 21 patients suffered from severe motor impairments,with GMFCS V in 18 cases.2.Genotype: PLA2G6 mutations were detected in 23 individuals by DNA sequencing,24 mutations were identified,with 12 novel mutations.In 7 patients,mutation was found only in 1 allele.Copy number variation of PLA2G6 was not detected in any patients either with mutation in only 1 allele or without mutations.Conclusions This is an important largest report on INAD in China.The 12 novel mutations expan-ded the PLA2G6 mutation spectrum.The research will enhance understanding of pediatrician to this rare disease and be helpful for the genetic counseling and prenatal diagnosis in China.