GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings.

[gm1 gangliosidosis]

GM 1 gangliosidosis and Morquio B syndrome , both arising from beta -galactosidase (GLB 1 ) deficiency , are very rare lysosomal storage diseases with an incidence of about 1 :100 ,000 -1 :200 ,000 live births worldwide . Here we report the beta -galactosidase gene (GLB 1 ) mutation analysis of 21 unrelated GM 1 gangliosidosis patients , and of 4 Morquio B patients , of whom two are brothers . Clinical features of the patients were collected and compared with those in literature . In silico analyses were performed by standard alignments tools and by an improved version of GLB 1 three -dimensional models . The analysed cohort includes remarkable cases . One patient with GM 1 gangliosidosis had a triple X syndrome . One patient with juvenile GM 1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B . A patient with infantile GM 1 gangliosidosis carried a complex GLB 1 allele harbouring two genetic variants leading to p .R 68 W and p .R 109 W amino acid changes , in trans with the known p .R 148 C mutation . Molecular analysis showed 27 mutations , 9 of which are new : 5 missense , 3 microdeletions and a nonsense mutation . We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses . Three -dimensional structural analysis of GLB 1 homology models including the new missense mutations and the p .R 68 W and p .R 109 W amino acid changes showed that all the amino acid replacements affected the resulting protein structures in different ways , from changes in polarity to folding alterations . Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM 1 gangliosidosis and Morquio B disease .

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gm1 gangliosidosis

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