Navegando por Palavras-chave "Mutation analysis"

Agora exibindo 1 - 2 de 2
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Novel GAA mutations in patients with Pompe disease
    (Elsevier B.V., 2015-04-25) Turaca, Lauro Thiago [UNIFESP]; Soares de Faria, Douglas Oliveira [UNIFESP]; Kyosen, Sandra Obikawa [UNIFESP]; Teixeira, Valber Dias [UNIFESP]; Motta, Fabiana Louise [UNIFESP]; Pessoa, Juliana Gilbert [UNIFESP]; Rodrigues e Silva, Marina [UNIFESP]; Almeida, Sandro Soares de [UNIFESP]; D'Almeida, Vania [UNIFESP]; Munoz Rojas, Maria Veronica; Martins, Ana Maria [UNIFESP]; Pesquero, Joao Bosco [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Genzyme Brasil A Sanofi Co
    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. (C) 2015 Elsevier B.V. All rights reserved.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations
    (Dr Dietrich Steinkopff Verlag, 2009-11-01) Oba-Shinjo, Sueli Mieko [UNIFESP]; Silva, Roseli da [UNIFESP]; Andrade, Fernanda G.; Palmer, Rachel E.; Pomponio, Robert J.; Ciociola, Kristina M.; Carvalho, Mary S.; Gutierrez, Paulo S.; Porta, Gilda; Marrone, Carlo D.; Munoz, Veronica; Grzesiuk, Anderson K.; Llerena, Juan C.; Berditchevsky, Celia R.; Sobreira, Claudia; Horovitz, Dafne; Hatem, Thamine P.; Frota, Elizabeth R. C.; Pecchini, Rogerio; Kouyoumdjian, Joao Aris; Werneck, Lineu Cesar [UNIFESP]; Amado, Veronica Moreira [UNIFESP]; Camelo, Jose S.; Mattaliano, Robert J.; Marie, Suely K. N.; 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)
    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.