Three novel homozygous mutations in the GNPTG gene that cause mucolipidosis type III gamma |
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Authors: | Shuang Liu Weimin Zhang Huiping Shi Yan Meng Zhengqing Qiu |
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Affiliation: | 1. Department of Pediatrics, PUMC Hospital, CAMS&PUMC, Beijing 100730, PR China;2. Clinical Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China;3. Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, PR China |
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Abstract: | BackgroundMucolipidosis 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.MethodsThree 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.ResultsThe 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.ConclusionsMutation 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. |
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Keywords: | A, adenosine α, alpha bp, base pair(s) β, beta C, cytidine cDNA, DNA complementary to RNA dNTP, deoxyribonucleoside triphosphate G, guanosine γ, gamma GlcNAc-1-phosphotransferase, N-acetylglucosamine-1-phosphotransferase GNPTAB, gene encoding the alpha/beta subunit of the N-acetylglucosamine-1-phosphotransferase GNPTG, gene encoding the gamma subunit of the N-acetylglucosamine-1-phosphotransferase kb, kilobase(s) or 1000 bp kDa, kilodalton(s) Km, kanamycin MLIII, mucolipidosis type III M6P, mannose-6-phosphate MW, molecular weight NMD, nonsense-mediated mRNA decay NN, Neural Network ORF, open reading frame T, thymidine Wt, wild type |
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