Identification of predominant GNPTAB gene mutations in Eastern Chinese patients with mucolipidosis Ⅱ/Ⅲ and a prenatal diagnosis of mucolipidosis Ⅱ

• 来源期刊: 中国药理学报（英文版）
• 关键词: mucolipidosis lysosomal enzymes genotype GNPTAB GNPTG gene mutation phenotype prenatal diagnosis
• 年，卷（期）: 2019,（2）
• 页码范围: 279-287
• 页数: 9页
• 语种: 英文

摘要

Mucolipidosis Ⅱ α/β,mucolipidosis Ⅲ α/β,and mucolipidosis Ⅲ y are autosomal recessive disorders belonging to the family of lysosomal storage disorders caused by deficiency of the UDP-N-acetylglucosamine,a lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GIcNAc-phosphotransferase) localized in the Golgi apparatus,which is essential for normal processing and packaging of soluble lysosomal enzymes with initiating the first step of tagging lysosomal enzymes with mannose-6-phosphate (M6P).Mucolipidosis Ⅱ and Ⅲ are caused by mutations in the GNPTAB and 6NPTG genes,and patients with these diseases are characterized by short stature,skeletal abnormalities,and developmental delay.In this study we report 38 patients with mucolipidosis Ⅱ and Ⅲ enrolled in Eastern China during the past 8 years.The diagnosis was made based on clinical characteristics and measurement of plasma lysosomal enzyme activity.Sanger sequencing of 6NPTAB and/or GNPTG for all patients and real-time quantitative PCR were performed to confirm the diagnosis.In addition,11 cases of prenatal mucolipidosis Ⅱ were diagnosed based on measurement of the enzyme activity in amniotic fluid supernatant and genetic testing of cultured amniotic cells.Based on molecular genetic tests,30 patients were diagnosed with mucolipidosis Ⅱ α/β,6 were diagnosed with Ⅲ α/β and 2 were diagnosed with Ⅲ γ.Thirty-seven different GNPTAB gene mutationswere identified in 29 patients with mucolipidosis Ⅱ α/β and six patients with Ⅲ α/β.These mutations included 22 new mutations (p.W44X,p.E279X,p.W416X,p.W463X,p.Q802X,p.Q882X,p.A34P,p.R334P,p.D408N,p.D534N,p.Y997C,p.D1018V,p.L1025S,p.L1033P,c.88_89delAC,c.890_891 insT,c.1150_1151 insTTA,c.1523delG,c.2473_2474insA,c.2980_2983delGCCT,c.3094delA,and deletion of exon 9).Four new GNPTG gene mutations were identified (c.13delC,p.Y81X,p.G126R and c.609+1delG) in two mucolipidosis Ⅲ y patients.Among the 11 cases of prenatal diagnosis,four were mucolipidosis Ⅱ fetuses,three were heterozygous,and the remaining four were normal fetuses.This study expands the mutation spectrum of the GNPTAB and GNPTG genes and contributes to specific knowledge of mucolipidosis Ⅱ/Ⅲ in a population from Eastern China.