Shuang Liu1, Weimin Zhang2, Huiping Shi3, Yan Meng3, Zhengqing Qiu4. 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. 4. Department of Pediatrics, PUMC Hospital, CAMS&PUMC, Beijing 100730, PR China. Electronic address: zhengqingqiu33@aliyun.com.
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.
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: M Hashim Raza; Carlos E F Domingues; Ronald Webster; Eduardo Sainz; Emily Paris; Rachel Rahn; Joanne Gutierrez; Ho Ming Chow; Jennifer Mundorff; Chang-Soo Kang; Naveeda Riaz; Muhammad A R Basra; Shaheen Khan; Sheikh Riazuddin; Danilo Moretti-Ferreira; Allen Braun; Dennis Drayna Journal: Eur J Hum Genet Date: 2015-07-01 Impact factor: 4.246
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