Mutation analysis and pathogenicity identification of Mucopolysaccharidosis type IVA in 8 south China families

Mucopolysaccharidosis type IVA (MPS IVA) is a rare autosomal recessive lysosomal storage disorder caused by GALNS gene mutation. The aim of our study is to detect pathogenic variants for patients suspected of MPS IVA and set the base for subsequent prenatal diagnosis and preimplantation genetic diagnosis.In our study, 9 MPS IVA patients from south China families were investigated. Urine glycosaminoglycans (GAGS) screening was used as an initial method. For patients with abnormal result, all 14 exons and intron-exon junctions of the GALNS gene were sequenced after amplification from genomic DNA. The pathogenicity of novel mutations were analyzed with molecular genetics, bioinformatics and structure modeling in light of clinical manifestations and biochemical results.Among 12 mutations detected, direct sequencing found 3 novel mutations (c.686A>C, p.Y229S; c.1498G>T, p.G500C; c.278T>C, p.I93T). The pathogenicity of these novel mutations was illustrated by correlating clinical symptoms with pedigree analysis and bioinformatics analysis.The detection and variant analysis are essential for accurate diagnosis of MPS IVA patients. Our results enrich GALNS gene mutation spectrum of Chinese population. This information has important clinical value for molecular diagnosis and genetic counseling of patients with this disease.