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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.
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.
摘要：
背景：III型粘脂症γ（MLIIIγ）是由GNPTG基因突变引起的常染色体隐性遗传疾病，编码N-乙酰葡糖胺-1-磷酸转移酶（GlcNAc-1-磷酸转移酶）的γ亚基。该蛋白质在溶酶体水解酶向溶酶体的转运中起关键作用。
方法：确定了三个典型的MLIII骨骼异常的中国儿童，他们来自无关的近亲家庭。在获得知情同意后，从患者及其父母中分离基因组DNA.使用标准PCR反应对GNPTG和GNPTAB基因进行直接测序。
结果：三个先证者表现出典型的MLIIIγ的临床特征，如关节僵硬和脊柱侧凸没有粗糙的面部特征。对GNPTG基因的突变分析显示鉴定出三个新的突变,第7外显子中的2个[c.425G>A（第Cys142Val）]和[c.515dupC（p。His172Profs27X)],和一个在外显子八[c.609+1G>C]。当与NCBI上的GenBank中的参考序列相比时,确定它们的亲本是杂合携带者。
结论：GNPTG基因突变是我们患者MLIIIγ的原因。我们的发现扩展了GNPTG基因的突变谱，并扩展了该疾病的表型-基因型相关性的知识。
方法：确定了三个典型的MLIII骨骼异常的中国儿童，他们来自无关的近亲家庭。在获得知情同意后，从患者及其父母中分离基因组DNA.使用标准PCR反应对GNPTG和GNPTAB基因进行直接测序。
结果：三个先证者表现出典型的MLIIIγ的临床特征，如关节僵硬和脊柱侧凸没有粗糙的面部特征。对GNPTG基因的突变分析显示鉴定出三个新的突变,第7外显子中的2个[c.425G>A（第Cys142Val）]和[c.515dupC（p。His172Profs27X)],和一个在外显子八[c.609+1G>C]。当与NCBI上的GenBank中的参考序列相比时,确定它们的亲本是杂合携带者。
结论：GNPTG基因突变是我们患者MLIIIγ的原因。我们的发现扩展了GNPTG基因的突变谱，并扩展了该疾病的表型-基因型相关性的知识。
