title: Three novel homozygous mutations in the GNPTG gene that cause mucolipidosis type III gamma.
abstract: BACKGROUND
  Mucolipidosis type III gamma (MLIII gamma) is an autosomal recessive disease caused by a mutation in the GNPTG gene, which encodes the γ subunit of the N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase). This protein plays a key role in the transport of lysosomal hydrolases to the lysosome.
  
  
  METHODS
  Three Chinese children with typical skeletal abnormalities of MLIII were identified, who were from unrelated consanguineous families. After obtaining informed consent, genomic DNA was isolated from the patients and their parents. Direct sequencing of the GNPTG and GNPTAB genes was performed using standard PCR reactions.
  
  
  RESULTS
  The three probands showed clinical features typical of MLIII gamma, such as joint stiffness and vertebral scoliosis without coarsened facial features. Mutation analysis of the GNPTG gene showed that three novel mutations were identified, two in exon seven [c.425G>A (p.Cys142Val)] and [c.515dupC (p.His172Profs27X)], and one in exon eight [c.609+1G>C]. Their parents were determined to be heterozygous carriers when compared to the reference sequence in GenBank on NCBI.
  
  
  CONCLUSIONS
  Mutation of the GNPTG gene is the cause of MLIII gamma in our patients. Our findings expand the mutation spectrum of the GNPTG gene and extend the knowledge of the phenotype-genotype correlation of the disease.
authors: Department of Pediatrics, PUMC Hospital, CAMS&PUMC, Beijing 100730, PR China.
authors: Shuang
authors: S
authors: Liu
authors: Clinical Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors: Weimin
authors: W
authors: Zhang
authors: Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, PR China.
authors: Huiping
authors: H
authors: Shi
authors: Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, PR China.
authors: Yan
authors: Y
authors: Meng
authors: Department of Pediatrics, PUMC Hospital, CAMS&PUMC, Beijing 100730, PR China. Electronic address: zhengqingqiu33@aliyun.com.
authors: Zhengqing
authors: Z
authors: Qiu
mesh_terms: D000293:Adolescent; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D009081:Mucolipidoses / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics*
chemical_list: D017855:Transferases (Other Substituted Phosphate Groups); C504791:GNPTG protein, human
keywords: A; C; DNA complementary to RNA; G; GNPTAB; GNPTG; GlcNAc-1-phosphotransferase; Km; M6P; MLIII; MW; Mucolipidosis type III; N-acetylglucosamine-1-phosphotransferase; NMD; NN; Neural Network; ORF; T; Wt; adenosine; alpha; base pair(s); beta; bp; cDNA; cytidine; dNTP; deoxyribonucleoside triphosphate; gamma; gene encoding the alpha/beta subunit of the N-acetylglucosamine-1-phosphotransferase; gene encoding the gamma subunit of the N-acetylglucosamine-1-phosphotransferase; guanosine; kDa; kanamycin; kb; kilobase(s) or 1000bp; kilodalton(s); mannose-6-phosphate; molecular weight; mucolipidosis type III; nonsense-mediated mRNA decay; open reading frame; thymidine; wild type; α; β; γ