title: Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations.
abstract: Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.
authors: Myopathies and Molecular Biology Group, Department of Neurology, School of Medicine, University of São Paulo, Av Dr Arnaldo, 455, 4th Floor, Room 4110, São Paulo, SP 01246-903, Brazil.
authors: Sueli M
authors: SM
authors: Oba-Shinjo
authors: Roseli
authors: R
authors: da Silva
authors: Fernanda G
authors: FG
authors: Andrade
authors: Rachel E
authors: RE
authors: Palmer
authors: Robert J
authors: RJ
authors: Pomponio
authors: Kristina M
authors: KM
authors: Ciociola
authors: Mary
authors: M
authors: S Carvalho
authors: Paulo S
authors: PS
authors: Gutierrez
authors: Gilda
authors: G
authors: Porta
authors: Carlo D
authors: CD
authors: Marrone
authors: Verônica
authors: V
authors: Munoz
authors: Anderson K
authors: AK
authors: Grzesiuk
authors: Juan C
authors: JC
authors: Llerena
authors: Célia R
authors: CR
authors: Berditchevsky
authors: Claudia
authors: C
authors: Sobreira
authors: Dafne
authors: D
authors: Horovitz
authors: Thamine P
authors: TP
authors: Hatem
authors: Elizabeth R C
authors: ER
authors: Frota
authors: Rogerio
authors: R
authors: Pecchini
authors: João Aris
authors: JA
authors: Kouyoumdjian
authors: Lineu
authors: L
authors: Werneck
authors: Veronica M
authors: VM
authors: Amado
authors: José S
authors: JS
authors: Camelo
authors: Robert J
authors: RJ
authors: Mattaliano
authors: Suely K N
authors: SK
authors: Marie
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001938:Brazil / Q000453:epidemiology / Q000208:ethnology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D000520:alpha-Glucosidases