Mucolipidosis Type â…¢ Alpha/beta In A Chinese Family Is Associated With Gnptab

MLⅢalpha/beta (MLⅢA, OMIM 252600) is a lysosomal storage diseases, which is also known as autosomal recessive inherited disease caused by deficiency of lysosomal enzyme N-acetylglucosamine-1 -phosphotransferase (GlcNAc- phosphotransferase, GlcNAc-PT). In the case of MLⅢ,the defective enzyme can't entry the lysosomal. GlcNac-1-phosphotransferase exists as a heterohexamer comprising three subunits,α/βencoded by GNPTAB andγencoded by GNPTAG, respectively. Theα/βsubunits contain the catalytic site of the enzyme and are encoded by the GNPTAB gene. Mutations in the GNPTAB gene can cause MLⅢ. In this thesis, we identified and characterized a four-generation Chinese family, in which 4 patients display symptom of Mucolipidosis.Linkage and haplotype analysis mapped the disease gene of this Chinese family to chromosome 12 with marker D20S346, where GNPTAB habored. DNA sequence for the whole coding region and exon-intron boundries of GNPTAB revealed compound heterozygous mutations in the family, a splicing mutation IVS13+1G>A (c.2715+1G>A), and a novel nonsense mutation p.R364X (c.1090C>T). All 4 patients in the family carry both of the GNPTAB mutations. The novel p.R364X mutation did not exist in unaffected family members and 226 normal controls. The IVS13+1G>A (c.2715+1G>A) mutation causes skipping of exon 12 directly onto exon 14 due to a deletion of 1103bp of exon 13 as previous reports, while p.R364X truncates the protein in theα-subunit, yielding truncatedα-subunit and noβ- subunit of GNPTAB. This study is the first report that compound heterozygotes of mutations in GNPTAB may cause MLⅢin Chinese and it expands the spectrum of mutations in GNPTAB causing MLⅢ. Further studies for the two mutations might help to understand the function of GNPTAB, and the relationship between GNPTAB mutations and the phenotypes of this disease.