title: Novel GAA mutations in patients with Pompe disease.
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 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.
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Lauro Thiago
authors: LT
authors: Turaça
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Douglas Oliveira Soares
authors: DO
authors: de Faria
authors: Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Sandra Obikawa
authors: SO
authors: Kyosen
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Valber Dias
authors: VD
authors: Teixeira
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Fabiana Louise
authors: FL
authors: Motta
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Juliana Gilbert
authors: JG
authors: Pessoa
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Marina
authors: M
authors: Rodrigues E Silva
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Sandro Soares
authors: SS
authors: de Almeida
authors: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Vânia
authors: V
authors: D'Almeida
authors: Personalized Genetic Health, Genzyme do Brasil-A Sanofi Company, São Paulo, SP, Brazil.
authors: Maria Verônica
authors: MV
authors: Munoz Rojas
authors: Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Ana Maria
authors: AM
authors: Martins
authors: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil. Electronic address: jbpesquero@unifesp.br.
authors: João Bosco
authors: JB
authors: Pesquero
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001938:Brazil; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D042241:Early Diagnosis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006003:Glycogen / Q000378:metabolism*; D006009:Glycogen Storage Disease Type II / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009123:Muscle Hypotonia / Q000235:genetics; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D044465:White People / Q000235:genetics; D055815:Young Adult; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D006003:Glycogen; C509951:GAA protein, human; D000520:alpha-Glucosidases
keywords: Acid alpha-glucosidase deficiency; Brazilian families; GAA gene; Mutation analysis; Pompe disease