RESUMO
GM1 gangliosidosis is a lysosomal storage disorder, characterized by psychomotor deterioration, visceromegaly, facial coarseness, retinal cherry-red spots, and skeletal abnormalities. We report six unrelated patients with GM1 gangliosidosis with extensive Mongolian spots on the trunk and extremities that provided clue to clinical diagnosis. All patients exhibited psychomotor delay, coarse facies, hepatosplenomegaly, hypotonia, and dysostosis multiplex. Four patients had retinal cherry-red spots. The condition was confirmed by identification of very low activities of beta-galactosidase enzyme in peripheral leukocytes and biallelic pathogenic variants in the GLB1 gene. We identified one novel (c.1479G>T) and two known (c.75 + 2dup and c.1369C>T) pathogenic variants in homozygous state in them. Our work ascertains extensive Mongolian spots as a diagnostic handle for early recognition of GM1 gangliosidosis. Though a known feature of GM1 gangliosidosis, considerable variation in the prevalence and ethnic differences are observed. This report illustrates the Mongolian spots pictorially in Indian patients.
Assuntos
Gangliosidose GM1/diagnóstico , Gangliosidose GM1/genética , Mancha Mongólica/diagnóstico , Mancha Mongólica/genética , Mutação , Fenótipo , Alelos , Estudos de Associação Genética , Predisposição Genética para Doença , Homozigoto , Humanos , Índia , Leucócitos/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismoAssuntos
Antipsicóticos/administração & dosagem , Proteínas do Tecido Nervoso/genética , Receptores de Dopamina D4/genética , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Proteínas do Tecido Nervoso/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D4/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/metabolismoRESUMO
BACKGROUND: Genetic variations represented as single nucleotide polymorphisms (SNPs) vary across the world population. This genetic polymorphism (such as SNPs) plays an important role in pharmacogenomics. SNPs that affects cellular metabolism, by altering the enzyme activity, have an important role in therapeutic outcome. Allele frequencies in number of clinically relevant SNPs within south Indian populations are not yet known. Hence, we genotyped randomly selected unrelated south Indian subjects from different locations of south India representing the heterogeneous ethnic background of the population. MATERIALS AND METHODS: Common variants of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULT1A1 gene polymorphisms were screened from healthy unrelated south Indian volunteers. Genotypes were determined using RFLP analysis of polymerase chain reaction-amplified products and confirmed by DNA sequencing. Chi-square test was performed to test for deviation from the Hardy-Weinberg equilibrium for each locus. RESULTS: Gene allele frequency for several polymorphisms in our study differed significantly between the populations of other nations reported for several of the SNPs. These results demonstrate that the populations in different geographic regions may have widely varying genetic allele frequencies for clinically relevant SNPs. CONCLUSION: The present study reports, for the first time, the frequency distribution of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULTIA1 gene polymorphisms in a south Indian population. Population-specific genetic polymorphism studies will help in practicing pharmacogenomic principles in the clinics.
