• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.13-16
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• 2016

Mucolipidosis (ML) II/III are autosomal recessive diseases caused by deficiency of post-translational modification of lysosomal enzymes. The mannose-6-phosphate (M6P) residue in lysosomal enzymes synthesized by N-acetylglucosamine 1-phosphotransferase (GlcNAc-phosphotransferase) serves as recognition marker for trafficking in lysosomes. GlcNAc-phosphotransferase is encoded by GNPTAB and GNPTG. Mutations in GNPTAB cause severe ML II alpha/beta and the attenuated ML III alpha/beta. Whereas mutations in GNPTG cause the ML III gamma, the attenuated type of ML III variant. For the diagnostic approaches, increased urinary oligosaccharides excretion could be a screening test in clinically suspicious patients. To confirm the diagnosis, instead of measuring the activity of GlcNAc phosphotransferase, measuring the enzymatic activities of different lysosomal hydrolases are useful for diagnosis. The activities of several lysosomal hydrolases are decreased in fibroblasts but increased in serum of the patients. In addition, the sequence analysis of causative gene is warranted. Therefore, the confirmatory diagnosis requires a combination of clinical evaluation, biochemical and molecular genetic testing. ML II/III show complex disease manifestations with lysosomal storage as the prime cellular defect that initiates consequential organic dysfunctions. As there are no specific therapy for ML to date, understanding the molecular pathogenesis can contribute to develop new therapeutic approaches ultimately.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.65-75
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• 2005

Purpose: To understand genetic differences and similarities between mucolipidosis and control. Methods: Using the fibroblast of the mucolipidosis II and control, forward and reverse subtracted libraries were constructed. Among these clones, we investigated mutations in the GNPTA (MGC4170) gene, which codes for the ${\alpha}/{\beta}$ subunits of phosphotransferase, and in the GNPTAG gene, which codes for the ${\gamma}$ subunits in 5 Korean patients with mucolipidosis type II or IIIA. Result: Several differentially expressed cDNAs were cloned and their sequences were determined. Mutation analysis of the interested gene, GNPTA was performed and we identified 7 mutations in the GNPTA gene, but none in the GNPTAG gene. The mutations in type II patients included p.Q104X(c.310C>T), p.R1189X(c.3565C>T), p.S1058X(c.3173C>G), p.W894X(c.2681G>A) and p.H1158fsX15(c.3474_3475delTA), all of which are non-sense or frame shift mutations. However, a splicing site mutation, IVS13+1G>A (c.2715+1G>A) was detected along with a non-sense or a frame shift mutation (p.R1189X or p.E858fsX3(c.2574_2575delGA)) in two mucolipidosis type IIIA patients. Conclusion: This report shows that mutations in the GNPTA gene coding for the ${\alpha}{\beta}$subunits of phosphotransferase, and not mutations in the GNPTAG gene, account for most of mutations found in Korean patients with mucolipidosis type II or IIIA.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.19-22
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• 2016

Purpose: Mucolipidosis type II (ML II), also known as I-cell disease is an autosomal recessive inherited disorder of lysosomal enzyme transport caused by a deficiency of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase). Clinical manifestations are skeletal abnormalities, mental retardation, cardiac disease, and respiratory complications. A severely and rapidity progressive clinical course leads to death before 10 years of age. Methods/Results: In this study we diagnosed three cases of prenatal ML II in two different at-risk families. We compared two procedures -biochemical analysis and molecular analysis - for the prenatal diagnosis of ML II. Both methods require an invasive procedure to obtain specimens for the diagnosis. Biochemical analysis requires obtaining cell cultures from amniotic fluid for more than two weeks, and would result in a late diagnosis at 19 to 22 weeks of gestation. Molecular genetic testing by direct sequence analysis is usually possible when mutations are confirmed in the proband. Molecular analysis has an advantage in that it can be performed during the first-trimester. Conclusion: Molecular diagnosis is a preferable method when a prompt decision is necessary.