Novel GAA mutations in patients with Pompe disease.

Article Details


Turaca LT, de Faria DO, Kyosen SO, Teixeira VD, Motta FL, Pessoa JG, Rodrigues E Silva M, de Almeida SS, D'Almeida V, Munoz Rojas MV, Martins AM, Pesquero JB

Novel GAA mutations in patients with Pompe disease.

Gene. 2015 Apr 25;561(1):124-31. doi: 10.1016/j.gene.2015.02.023. Epub 2015 Feb 12.

PubMed ID
25681614 [ View in PubMed

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.

DrugBank Data that Cites this Article

NameUniProt ID
Lysosomal alpha-glucosidaseP10253Details