Novel GAA mutations in patients with Pompe disease

作者：Turaca Lauro Thiago; Soares de Faria Douglas Oliveira; Kyosen Sandra Obikawa; Teixeira Valber Dias; Motta Fabiana Louise; Pessoa Juliana Gilbert; Rodrigues e Silva Marina; de Almeida Sandro Soares; D'Almeida Vania; Munoz Rojas Maria Veronica; Martins Ana Maria; Pesquero Joao Bosco^*

来源：Gene, 2015, 561(1): 124-131.

DOI：10.1016/j.gene.2015.02.023

• Acid alpha-glucosidase deficiency
• Pompe disease
• Mutation analysis
• Brazilian families
• GAA gene

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.

• 出版日期2015-4-25