제2형 점액지질증 한국인 환자에서 보고된 GNPTAB 유전자의 새로운 돌연변이
Identification of a novel GNPTAB gene mutation in a Korean patient with Mucolipidosis type II
Abstract
Objective: Mucolipidosis type II alpha/beta (ML II; I-cell disease) is a rare, inherited, metabolic disease and has often been clinically misdiagnosed. ML II results from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-PT), which causes the lysosomal enzymes to accumulate in plasma. The phenotype of ML II, a disorder of lysosomal enzyme transport, includes mucopolysaccharidosis type I (Hurler syndrome)-like features and dysostosis multiplex, usually apparent after 6 months of age. We report here a male patient with ML II. Methods: We retrospectively investigated the clinical, biochemical, and genetic characterization of a patient with suspected ML II in Pusan National University Children’s Hospital. Mutation in the GNPTAB gene was analyzed using direct DNA sequencing. Results: A boy, aged 10 years 11 months, was presented with short stature. The patient was first baby of non-consanguineous Korean parents. He was born at gestational age of 40 weeks with 3580 grams of weight. His height was 82.4cm (3th percentile). The patient had clinical features commonly found in ML II, including disproportionate dwarfism, retarded psychomotor development, coarse facial features, gibbous and restricted joint mobility. The diagnosis was proved by an extremely elevated activity of lysosomal enzymes in the serum. Genetic analysis of GNPTAB revealed compound heterozygous mutations, c.2990A>G (p.Tyr997Cys) and c.3565C>T (p.Arg1189*), the former of which is a novel mutation. These compound heterozygous mutations were derived from his mother (p.Tyr997Cys) and his father (p.Arg1189*), respectively. CONCLUSIONS: To our knowledge, c.2990A>G mutation has not been previously reported. Our findings add to the number of reported cases of this rare illness and to the GNPTAB pathogenic mutation database.