Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations

Author Oba-Shinjo, Sueli M. Google Scholar
Silva, Roseli da Google Scholar
Andrade, Fernanda G. Google Scholar
Palmer, Rachel E. Google Scholar
Pomponio, Robert J. Google Scholar
Ciociola, Kristina M. Google Scholar
Carvalho, Mary S. Google Scholar
Gutierrez, Paulo S. Google Scholar
Porta, Gilda Google Scholar
Marrone, Carlo D. Google Scholar
Munoz, Veronica Google Scholar
Grzesiuk, Anderson K. Google Scholar
Llerena, Juan C. Google Scholar
Berditchevsky, Celia R. Google Scholar
Sobreira, Claudia Google Scholar
Horovitz, Dafne Google Scholar
Hatem, Thamine P. Google Scholar
Frota, Elizabeth R. C. Google Scholar
Pecchini, Rogerio Google Scholar
Kouyoumdjian, Joao Aris Google Scholar
Werneck, Lineu Google Scholar
Amado, Veronica M. Google Scholar
Camelo, Jose S. Google Scholar
Mattaliano, Robert J. Google Scholar
Marie, Suely K. N. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Genzyme Corp
Clin Marrone
Hosp Clin Porto Alegre
Inst Neurol & Coluna Vertebral
Fundacao Oswaldo Cruz
Hosp Servidores Estado Rio de Janeiro
Unidade Cardiol & Med Fetal
Universidade Federal de Minas Gerais (UFMG)
Santa Casa de Misericordia Med Sch
Sch Med Sao Jose do Rio Preto
Univ Parana
Universidade de Brasília (UnB)
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.
Keywords Acid alpha-glucosidase
Pompe disease
Glycogen storage disease type II
Acid maltase deficiency
Mutation analysis
Novel mutation
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Genzyme Corporation
Grant number FAPESP: 2001/00422-5
Date 2009-11-01
Published in Journal of Neurology. Heidelberg: Dr Dietrich Steinkopff Verlag, v. 256, n. 11, p. 1881-1890, 2009.
ISSN 0340-5354 (Sherpa/Romeo, impact factor)
Publisher Dr Dietrich Steinkopff Verlag
Extent 1881-1890
Origin http://dx.doi.org/10.1007/s00415-009-5219-y
Access rights Closed access
Type Article
Web of Science ID WOS:000271079200013
URI http://repositorio.unifesp.br/handle/11600/31915

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