Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.
Mucolipidosis types II and III are autosomal recessive inherited diseases caused by a deficiency in the lysosomal enzyme N-acetylglucosamine-1 phosphotransferase (GlcNAc-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 II or IIIA. We identified seven mutations in the GNPTA gene, but none in GNPTAG. 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 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_2575delGA)) 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 II or IIIA.
Paik
Kyung Hoon
KH
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gang-Nam Gu, Seoul, 135-710, Korea.
Song
Seng Mi
SM
Ki
Chang Seok
CS
Yu
Han-Wook
HW
Kim
Jung Sim
JS
Min
Ki Hoon
KH
Chang
Soo Hee
SH
Yoo
Eun Jae
EJ
Lee
In Jung
IJ
Kwan
Eun Kyung
EK
Han
Sun Joo
SJ
Jin
Dong-Kyu
DK
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009081:Mucolipidoses / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics* / Q000378:metabolism
D017855:Transferases (Other Substituted Phosphate Groups); C505859:alpha-beta GlcNAc-1-phosphotransferase, human; C511050:GNPTAB protein, human; C504791:GNPTG protein, human