Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase α/β subunits in Korean patients with mucolliplidoslis type II or type IIIA

Mucolipidosis types 11 and III are autosomal recessive inherited diseases caused by a deficiency in the lysosomal enzyme N-acetylglucosamine-1 phosphotransferase (G1cNAc-phosphotransferase), which adds phosphate to function as a recognition marker for the uptake and transport of lysosomal enzymes. 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 its gamma subunits in five Korean patients with mucolipidosis type 11 or IIIA. We identified seven mutations in the GNPTA gene, but none in GNPTAG. The mutations in type 11 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 nonsense or frameshift mutations. However, a splicing site mutation, IVS13+1G > A (c.2715+1G > A) was detected along with a nonsense or a frameshift mutation (p.R1189X or p.E858fsX3 (c.2574_2575de1GA)) in two mucolipidosis type IIIA patients. 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 the genetic mutations found in Korean patients with mucolipidosis type 11 or IIIA.