title: Two homozygous nonsense mutations of GNPTAB gene in two Chinese families with mucolipidosis II alpha/beta using targeted next-generation sequencing.
abstract: Mucolipidosis II alpha/beta (ML II alpha/beta; I-cell disease) is a rare, inherited, metabolic disease and has often been clinically misdiagnosed. ML II alpha/beta results from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-PT), which causes the lysosomal enzymes to accumulate in plasma. We identified two new Chinese patients with ML II alpha/beta by lysosomal enzyme assay. Using targeted next-generation sequencing genetic analysis, we located two homozygous nonsense mutations in the GNPTAB gene, c.1071G>A (p.W357X) and c.1090C>T (p.R364X). These results were confirmed by Sanger sequencing. To our knowledge, the c.1071G>A mutation has not been previously reported. Our findings add to the number of reported cases of this rare illness and to the GNPTAB pathogenic mutation database. This work also demonstrates the application of lysosomal enzyme assay and targeted next-generation sequencing for the genetic screening analysis and diagnosis of ML II alpha/beta.
authors.affiliation: Department of Clinical Genetics, Bayi Children's Hospital Affiliated to General Hospital of Beijing Military Region, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Haihong
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Mancang
authors.initials: M
authors.lastname: Zhao
authors.forename: Xiyu
authors.initials: X
authors.lastname: He
mesh_terms: D002681:China; D018389:Codon, Nonsense; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009081:Mucolipidoses / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D017855:Transferases (Other Substituted Phosphate Groups); C511050:GNPTAB protein, human
keywords: Massively-parallel sequencing; Mucolipidosis; N-acetylglucosamine-1-phosphotransferase; Nonsense mutation