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Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.
- Source :
-
Journal of human genetics [J Hum Genet] 2009 Mar; Vol. 54 (3), pp. 145-51. Date of Electronic Publication: 2009 Feb 06. - Publication Year :
- 2009
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Abstract
- Mucolipidosis (ML) II alpha/beta and III alpha/beta are autosomal recessive diseases caused by a deficiency of alpha and/or beta subunits of the enzyme N-acetylglucosamine-1-phosphotransferase, which is encoded by the GNPTAB gene. We analyzed the GNPTAB gene in 25 ML II and 15 ML III Japanese patients. In most ML II patients, the clinical conditions 'stand alone', 'walk without support' and 'speak single words' were impaired; however, the frequency of 'heart murmur', 'inguinal hernia' and 'hepatomegaly and/or splenomegaly' did not differ between ML II and III patients. We detected mutations in GNPTAB in 73 of 80 alleles. Fourteen new mutations were c.914_915insA, c.2089_2090insC, c.2427delC, c.2544delA, c.2693delA, c.3310delG, c.3388_3389insC+c.3392C>T, c.3428_3429insA, c.3741_3744delAGAA, p.R334L, p.F374L, p.H956Y, p.N1153S and duplication of exon 2. Previously reported mutations were p.Q104X, p.W894X, p.R1189X and c.2715+1G>A causing skipping of exon 13. Homozygotes or compound heterozygotes of nonsense and frameshift mutations contributed to the severe phenotype. p.F374L, p.N1153S and splicing mutations contributed to the attenuated phenotype, although coupled with nonsense mutation. These results show the effective molecular diagnosis of ML II and III and also provide phenotypic prediction. This is the first and comprehensive report of molecular analysis for ML patients of Japanese origin.
- Subjects :
- Base Sequence
DNA Mutational Analysis
Exons genetics
Gene Duplication
Genotype
Humans
Molecular Sequence Data
Mutation genetics
Phenotype
Polymorphism, Single Nucleotide genetics
Asian People genetics
Mucolipidoses enzymology
Mucolipidoses genetics
Transferases (Other Substituted Phosphate Groups) genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1435-232X
- Volume :
- 54
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 19197337
- Full Text :
- https://doi.org/10.1038/jhg.2009.3