Molecular Analysis of 9 Unrelated Families Presenting With Juvenile and Chronic GM1 Gangliosidosis

Abstract

GM1 gangliosidosis is a rare autosomal recessive lysosomal storage disorder with high prevalence in Brazil (1:17 000). In the present study, we genotyped 10 individuals of 9 unrelated families from the States of São Paulo and Minas Gerais diagnosed with the juvenile and chronic forms of the disease. We found the previously described p.Thr500Ala mutation in 8 alleles; c.1622-1627insG and p.Arg59His in 2 alleles (the latter also segregating with c.1233+8T>C); and p.Phe107Leu, p.Leu173Pro, p.Arg201His, and p.Gly311Arg in 1 allele each. Two mutations (p.Ile354Ser and p.Thr384Ser) and 1 neutral alteration (p.Pro152=) are described for the first time. All patients presented as compound heterozygotes. A discussion on genotype–phenotype correlation is also presented.

Gene therapy approaches for GM1 gangliosidosis: Focus on animal and cellular studies

“…As a result, the frequency of mutations indicates diversity in the glb1 gene. 73 During the study of Ou et al, a method was used to prove the genotype-phenotype correlation using in silico tools. In this method, 38 US patients with GM1…”

“…The main clinical phenotype of all these patients was skeletal manifestations and neurological symptoms. As a result, the frequency of mutations indicates diversity in the glb1 gene 73 . During the study of Ou et al, a method was used to prove the genotype–phenotype correlation using in silico tools.…”

Re: “Molecular analysis of 9 unrelated families presenting with juvenile and chronic GM1 gangliosidosis”

“…Dear Editor, We have previously published in this Journal the results of a molecular study on a series of patients presenting with juvenile and chronic GM1 gangliosidosis; the method was target-gene analysis using Sanger sequencing for the 16 exons and their flanking regions of the GLB1 gene [1]. At that time, one of the individuals (patient 5) had only one variant identified, p.Thr500Ala, in the maternal allele.…”

Gangliosidose GM1

“…O conhecimento sobre os efeitos das alterações na função e biossíntese da proteína β-gal ainda é limitado 27 , dificultando uma clara relação genótipo/fenótipo. Outro fator que dificulta o esclarecimento dessa relação é a heterogeneidade molecular, a exemplo de um caso prévio de um paciente homozigoto para a mutação p.Arg201His sem envolvimento neurológico foi classificado com doença de Morquio B, outros heterozigotos com essa mutação foram associados com a forma juvenil ou adulta da gangliosidose GM1 27,34 .…”