Novel GAA mutations in patients with Pompe disease
| Autor: | Ana Maria Martins, Valber Dias Teixeira, Sandro Soares de Almeida, João Bosco Pesquero, Lauro Thiago Turaça, Maria Verônica Munoz Rojas, Sandra Obikawa Kyosen, Fabiana Louise Motta, Juliana Gilbert Pessoa, Vânia D'Almeida, Marina Rodrigues e Silva, Douglas Oliveira Soares de Faria |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Adolescent Nonsense mutation Mutation Missense Biology medicine.disease_cause White People Exon Young Adult Asian People Glycogen storage disease type II Genetics medicine Missense mutation Coding region Humans Genetic Predisposition to Disease Genetic Testing Child Gene Genetic Association Studies Sequence Deletion Mutation Base Sequence Glycogen Storage Disease Type II Infant alpha-Glucosidases General Medicine Sequence Analysis DNA Cardiomyopathy Hypertrophic Middle Aged medicine.disease Hypotonia Black or African American Early Diagnosis Codon Nonsense Child Preschool Muscle Hypotonia Female medicine.symptom Brazil Glycogen |
| Zdroj: | Gene. 561(1) |
| ISSN: | 1879-0038 |
| Popis: | Pompe disease is an autosomal recessive disorder linked to GAA gene that leads to a multi-system intralysosomal accumulation of glycogen. Mutation identification in the GAA gene can be very important for early diagnosis, correlation between genotype-phenotype and therapeutic intervention. For this purpose, peripheral blood from 57 individuals susceptible to Pompe disease was collected and all exons of GAA gene were amplified; the sequences and the mutations were analyzed in silico to predict possible impact on the structure and function of the human protein. In this study, 46 individuals presented 33 alterations in the GAA gene sequence, among which five (c.547-67C>G, c.547-39T>G, p.R437H, p.L641V and p.L705P) have not been previously described in the literature. The alterations in the coding region included 15 missense mutations, three nonsense mutations and one deletion. One insertion and other 13 single base changes were found in the non-coding region. The mutation p.G611D was found in homozygosis in a one-year-old child, who presented low levels of GAA activity, hypotonia and hypertrophic cardiomyopathy. Two patients presented the new mutation p.L705P in association with c.-32-13T>G. They had low levels of GAA activity and developed late onset Pompe disease. In our study, we observed alterations in the GAA gene originating from Asians, African-Americans and Caucasians, highlighting the high heterogeneity of the Brazilian population. Considering that Pompe disease studies are not very common in Brazil, this study will help to better understand the potential pathogenic role of each change in the GAA gene. Furthermore, a precise and early molecular analysis improves genetic counseling besides allowing for a more efficient treatment in potential candidates. |
| Databáze: | OpenAIRE |
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