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Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype–phenotype correlation.

Authors :
Otomo, Takanobu
Muramatsu, Takeshi
Yorifuji, Tohru
Okuyama, Torayuki
Nakabayashi, Hiroki
Fukao, Toshiyuki
Ohura, Toshihiro
Yoshino, Makoto
Tanaka, Akemi
Okamoto, Nobuhiko
Inui, Koji
Ozono, Keiichi
Sakai, Norio
Source :
Journal of Human Genetics; Mar2009, Vol. 54 Issue 3, p145-151, 7p, 5 Charts, 1 Graph
Publication Year :
2009

Abstract

Mucolipidosis (ML) II alpha/beta and III alpha/beta are autosomal recessive diseases caused by a deficiency of α and/or β 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.Journal of Human Genetics (2009) 54, 145–151; doi:10.1038/jhg.2009.3; published online 6 February 2009 [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14345161
Volume :
54
Issue :
3
Database :
Complementary Index
Journal :
Journal of Human Genetics
Publication Type :
Academic Journal
Accession number :
37158208
Full Text :
https://doi.org/10.1038/jhg.2009.3