Genotype-phenotype correlation of gangliosidosis mutations using in silico tools and homology modeling

Molecular Genetics and Metabolism Reports
Li OuJeanine R Jarnes-Utz

Abstract

Gangliosidoses, including GM1-gangliosidosis and GM2-gangliosidosis (Tay-Sachs disease and Sandhoff disease), are lysosomal disorders resulting from enzyme deficiencies and accumulation of gangliosides. Phenotypes of gangliosidoses range from infantile, late-infantile, juvenile, and to the adult form. The genotype-phenotype correlation is essential for prognosis and clinical care planning for patients with a gangliosidosis condition. Previously, we have developed a method to establish the genotype-phenotype correlation of another lysosomal disease, mucopolysaccharidosis type I, with in silico tools. This same method was applied to analyze the genotype and phenotype of 38 patients diagnosed with a gangliosidosis disease in the United States. Out of 40 mutations identified, 3 were novel, including p.Tyr192His and p.Phe556Ser of the GLB1 gene and p.Gly461Val of the HEXA gene. Furthermore, the mutant protein structure of all missense mutations was constructed by homology modeling. A systemic structural analysis of these models revealed the specific mechanisms of how each mutation may lead to the disease. In summary, the method developed in this study holds promise as a tool that can be broadly applicable to other lysosomal diseases...Continue Reading

References

Jan 1, 1992·Human Mutation·N AkalinF Kaplan
Nov 27, 1991·Biochemical and Biophysical Research Communications·P BanerjeeG Dawson
Jan 1, 1988·Journal of Neurochemistry·K Ohno, K Suzuki
May 31, 1968·Science·S Okada, J S O'Brien
Apr 1, 1995·Human Molecular Genetics·Z X ZhangR A Gravel
Jan 1, 1994·Journal of Inherited Metabolic Disease·A TanakaK Suzuki
Jan 1, 1993·Human Molecular Genetics·S AkliL Poenaru
Apr 1, 1995·Biochemical and Molecular Medicine·L PelegB Goldman
Jun 1, 1997·Journal of Child Neurology·E M KayeX O Breakefield
Dec 16, 1998·Molecular Genetics and Metabolism·H A Ozkara, R Navon
Apr 24, 2001·Human Mutation·A Alvarez-RodríguezC M Lozano
May 5, 2001·Genome Research·P C Ng, S Henikoff
Feb 16, 2005·Brain Research. Molecular Brain Research·Stephanos KyrkanidesHoward J Federoff
Jun 16, 2005·Archives of Neurology·Lauren C FreyChristopher M Filley
Jun 28, 2005·Nucleic Acids Research·Emidio CapriottiRita Casadio
Sep 10, 2005·Bone Marrow Transplantation·J F M JacobsP M Hoogerbrugge
Jan 24, 2007·The Journal of Biological Chemistry·Gustavo H B MaegawaDon J Mahuran
Mar 25, 2008·Pediatric Neurology·Alex R PaciorkowskiEdwin Kolodny
Oct 22, 2008·Molecular Genetics and Metabolism·S Z WangT M Cox
Jul 15, 2009·Molecular Genetics and Metabolism·Gustavo H B MaegawaJoe T R Clarke
Nov 10, 2009·Journal of Inherited Metabolic Disease·S B WortmannE Morava
Jan 27, 2010·Biochemical and Biophysical Research Communications·Carole GiraudCatherine Caillaud
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Apr 19, 2011·Biochimica Et Biophysica Acta·Anna CaciottiAmelia Morrone
Apr 27, 2011·Annals of Neurology·Daisuke TsujiKohji Itoh
Sep 23, 2011·Nature·Hossein NajmabadiH Hilger Ropers
Nov 26, 2011·Developmental Medicine and Child Neurology·Nicholas J SmithChristopher M Verity

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Methods Mentioned

BETA
metabolomics profiling
protein folding

Clinical Trials Mentioned

NCT00668187

Software Mentioned

Swiss
SIFT
PROVEAN
SAAMP
SNP
PDB viewer
PHD
SNPs
PolyPhen
PANTHER

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