Development of a feasible assay for the detection of GAA mutations in patients with Pompe disease

Er, Tze‐Kiong; Chen, Chih-Chieh; Chien, Yin‐Hsiu; Liang, Wen‐Chen; Kan, Tzu-Min; Jong, Yuh‐Jyh

doi:10.1016/j.cca.2013.10.013

Cited by 7 publications

(8 citation statements)

References 40 publications

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“…In particular, in the conserving profile of a protein, the residue of a lower conservation score is more conserved than that of a higher conservation score. 23 Indeed, Figure 2 shows that the rWCN profile and the conservation profile overlap extremely well in the IDH1, IDH2, and p53 proteins. Here, we show that among the pathogenic mutations, these residues (IDH1 R132H, IDH2 R172M, and p53 R175H) are conserved and located in more compact environments, so it is reasonable to assume that these mutations are strongly associated with the functionality and the structure of the protein.…”

Section: Resultsmentioning

confidence: 92%

“…In particular, in the conserving profile of a protein, the residue of a lower conservation score is more conserved than that of a higher conservation score. 23…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…A TM-score >0.5 indicates a model of correct topology like IDH1 TM = 0.90 ± 0.06, IDH2 TM = 0.61 ± 0.14, and p53 TM = 0.42 ± 0.14; however, in the case where the TM-score is <0.17, there is random similarity. 23,24 The modeled proteins are further validated by the Ramachandran plot generated by Procheck. The Ramachandran plot value for IDH1 ( Figure 3A) was found to be 91.8% with 628 residues lying in the favored region, 7.7% of the residues lying in the additional allowed region, and 0.4% lying in the generously allowed region.…”

Section: Resultsmentioning

confidence: 99%

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Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

et al. 2020

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Introduction: The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas. Methods: In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 ( IDH1) and isocitrate dehydrogenase 2 ( IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53. Results: We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein. Conclusion: In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.

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Section: Resultsmentioning

confidence: 92%

“…In particular, in the conserving profile of a protein, the residue of a lower conservation score is more conserved than that of a higher conservation score. 23…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

et al. 2020

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“…A amostra tecidual com mais alta atividade da enzima, e, portanto, melhor para o diagnóstico, é composta de fibroblastos da pele cultivados, mas também pode ser utilizado músculo, ambos os tecidos obtidos por biópsia (5). Adicionalmente, pode ser realizada a análise do tipo de mutação presente (6).…”

Section: Introductionunclassified

Tratamento Da Doença De Pompe - Deficiência Da Alfa-Glicosidase Ácida

Kuhn¹,

Borges²,

Bock³

2014

Infarma

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Este trabalho tem como objetivos descrever a patogênese e o tratamento da doença de Pompe. Foi realizado um estudo de revisão bibliográfica mediante busca de artigos científicos publicados entre 2004 e 2014. Portadores de deficiência na enzima alfa acido glicosidase, desenvolvem a doença de Pompe, que resulta em um acumulo de glicogênio dentro do lisossomo, originando danos e disfunções orgânicas no tecido muscular, ocasionando dificuldades na respiração, locomoção, fala e audição. A terapia de reposição enzimática é a alternativa de tratamento específica para Pompe, melhorando significativamente a função cardíaca e reduzindo a mortalidade. Contudo, a necessidade de injeção de altas doses da enzima, a perda de 80% da enzima por conta do metabolismo hepático e o alto custo do tratamento dificultam o seu uso. A dose que mostrou melhores resultados foi de 20 mg/kg da enzima a cada duas semanas. Todavia, apesar do alto custo do tratamento, os benefícios de diminuição de sintomas dos pacientes são importantes, como melhora na realização de atividades da vida diária, aumento da força muscular, redução da fadiga e incrementos na função pulmonar. Existem ainda, tratamentos alternativos, mas que ainda estão em fase de estudos. Dentre os tratamentos, aquele que possui um melhor prognóstico é a reposição com a enzima humana recombinante. A terapia de reposição enzimática trouxe sobrevida a diversos pacientes devido à diminuição da hipertrofia cardíaca e melhora nos sintomas motores.

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Clinical and GAA gene mutation analysis in 21 Chinese patients with classic infantile pompe disease

Sheng

Huang

et al. 2020

European Journal of Medical Genetics

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Development of a feasible assay for the detection of GAA mutations in patients with Pompe disease

Cited by 7 publications

References 40 publications

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

Tratamento Da Doença De Pompe - Deficiência Da Alfa-Glicosidase Ácida

Clinical and GAA gene mutation analysis in 21 Chinese patients with classic infantile pompe disease

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