Novel GAA mutations in patients with Pompe disease

Novel GAA mutations in patients with Pompe disease

Author Turaca, Lauro Thiago Autor UNIFESP Google Scholar
Soares de Faria, Douglas Oliveira Autor UNIFESP Google Scholar
Kyosen, Sandra Obikawa Autor UNIFESP Google Scholar
Teixeira, Valber Dias Autor UNIFESP Google Scholar
Motta, Fabiana Louise Autor UNIFESP Google Scholar
Pessoa, Juliana Gilbert Autor UNIFESP Google Scholar
Rodrigues e Silva, Marina Autor UNIFESP Google Scholar
Almeida, Sandro Soares de Autor UNIFESP Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Munoz Rojas, Maria Veronica Google Scholar
Martins, Ana Maria Autor UNIFESP Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Genzyme Brasil A Sanofi Co
Abstract 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 GM 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 GM 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 GM 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 GM activity, hypotonia and hypertrophic cardiomyopathy. Two patients presented the new mutation p1705P in association with c.-32-13T>G. They had low levels of GM activity and developed late onset Pompe disease. in our study, we observed alterations in the GM 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 GM gene. Furthermore, a precise and early molecular analysis improves genetic counseling besides allowing for a more efficient treatment in potential candidates. (C) 2015 Elsevier B.V. All rights reserved.
Keywords Acid alpha-glucosidase deficiency
Pompe disease
Mutation analysis
Brazilian families
GAA gene
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2008/06676-8
Date 2015-04-25
Published in Gene. Amsterdam: Elsevier B.V., v. 561, n. 1, p. 124-131, 2015.
ISSN 0378-1119 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 124-131
Access rights Closed access
Type Article
Web of Science ID WOS:000351976900018

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