Molecular analysis of the most prevalent mutations of the FANCA and FANCC genes in Brazilian patients with Fanconi anaemia

Rodriguez, David Enrique Aguilar; Lima, Carmen Sílvia Passos; Lourenço, Gustavo Jacob; Figueiredo, Maria Estela; Carneiro, Jorge David Aivazoglu; Tone, Luíz Gonzaga; Llerena, Juan Clinton; Toscano, Raquel Alves; Brandalise, Sílvia Regina; Júnior, Walter Pinto; Costa, Fernando Ferreira; Bertuzzo, Carmen Sílvia

doi:10.1590/s1415-47572005000200004

Cited by 5 publications

(7 citation statements)

References 30 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, 72.2% of the patients (n = 26) were found to have FANCC gene mutations, both homozygous and heterozygous. Similarly, in another study conducted in Brazil, FANCC gene mutations were found in two-thirds of the patients (17).…”

Section: Discussionmentioning

confidence: 54%

See 1 more Smart Citation

Analysis of FANCC gene mutations (IVS4+4A>T, del322G, and R548X)in patients with Fanconi anemia in Pakistan

Aftab¹,

Iram²,

Khaliq³

et al. 2017

Turk J Med Sci

View full text Add to dashboard Cite

Background/aim: Fanconi anemia (FA) is an autosomal recessive disease determined by mutations in at least 16 genes, with distinct distributions in different populations. To the best of our knowledge, there are no reports regarding the molecular basis of the disease in FA patients in Pakistan. The current study aimed to determine the frequency of FANCC gene mutations, i.e. IVS4+4A>T, del322G, and R548X, in FA patients.Materials and methods: Genomic DNA was obtained from 36 FA patients. All samples were analyzed by polymerase chain reaction and restriction fragment length polymorphism techniques.Results: Mutation IVS4+4A>T was identified in 26 (72.2%) patients. It was homozygous in 6 and heterozygous in 20 patients. Del322G and R548X were found with the following prevalences: del322G, 5.6%, and R548X, 5.6%. Patients with these two mutations were compound heterozygotes having concomitant IVS4+4A>T mutation. Conclusion:These results suggest that mutation IVS4+4A>T is the most prevalent mutation in our group of patients. This analysis of Pakistani patients also suggests that there is no significant difference between IVS4+4A>T homozygotes and the rest of the patients with regard to severity of clinical phenotype.

show abstract

Section: Discussionmentioning

confidence: 54%

“…The same results were confirmed by the IFAR (18). In another study, it was reported that IVS4+4A>T was the most prevalent mutation of the FANCC gene and it was detected in 15.9% of Brazilian FA patients (17). The same mutation was also present in 31% of Japanese patients.…”

Section: Discussionmentioning

confidence: 90%

Analysis of FANCC gene mutations (IVS4+4A>T, del322G, and R548X)in patients with Fanconi anemia in Pakistan

Aftab¹,

Iram²,

Khaliq³

et al. 2017

Turk J Med Sci

View full text Add to dashboard Cite

show abstract

“…Given the importance of identifying these patients and the lack of studies conducted in Brazil mainly focused on their clinical characteristics (10)(11)(12)(13)(14)(15) , the objective of the present study was to characterize the clinical profile of patients diagnosed with FA seen at a clinical genetics department.…”

Section: Introductionmentioning

confidence: 99%

Características clínicas de pacientes com anemia de Fanconi

Zen

Moraes

Rosa

et al. 2011

Rev. paul. pediatr.

View full text Add to dashboard Cite

OBJETIVO: Verificar as características clínicas de pacientes com anemia de Fanconi (AF) diagnosticados em um Serviço de Genética Clínica. MÉTODOS: O estudo incluiu todos os pacientes atendidos no Serviço de Genética Clínica da Universidade Federal de Ciências da Saúde de Porto Alegre e Complexo Hospitalar Santa Casa de Porto Alegre, entre 1975 e 2008, com suspeita clínica de AF submetidos ao estudo de quebras cromossômicas com o uso de diepoxi-butano (DEB) a partir do sangue periférico. Realizou-se uma análise retrospectiva das características clínicas dos pacientes, a partir de um levantamento sistemático dos seus prontuários médicos. RESULTADOS: A amostra foi composta de 17 pacientes, sendo que em sete o diagnóstico de AF foi confirmado. Os pacientes com AF caracterizaram-se por um fenótipo amplo, oscilando desde um quadro de pancitopenia sem dismorfias até a presença de múltiplas malformações sem alterações hematológicas. Certos achados, como face triangular, orelhas em abano e manchas café com leite foram frequentes e encontrados apenas nos indivíduos com AF. História de equimoses, hematomas, petéquias, infecções e linfadenopatias foi comum entre os indivíduos desse grupo. Por outro lado, alterações neurológicas foram observadas apenas em pacientes sem AF. Consanguinidade foi verificada em apenas um paciente, que apresentava AF. CONCLUSÕES: Apesar das limitações do estudo, os achados ilustram a grande variabilidade fenotípica observada na AF, o que torna seu diagnóstico clínico um desafio. No entanto, alguns achados específicos podem servir de pistas para sua detecção. A identificação precoce desses indivíduos é fundamental para o seu manejo adequado.

show abstract

“…All of these have been reported as germline mutations, resulting in an in-frame deletion of phenylalanine at a position that is conserved across species. This particular mutation has been reported as homozygous or compound heterozygous with other pathogenic variants in numerous FA patients [ 27 – 29 ]. Experimental studies have shown that this sequence change alters nuclear localization of FANCA protein and impairs the function of FANCA in vitro, and therefore this variant has been classified as pathogenic [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Novel FANCA mutation in the first fully-diagnosed patient with Fanconi anemia in Polish population – case report

et al. 2020

View full text Add to dashboard Cite

Background: Fanconi anemia is a rare genetic disorder caused by mutations in genes which protein products are involved in replication, cell cycle control and DNA repair. It is characterized by congenital malformations, bone marrow failure, and high risk of cancer. The diagnosis is based on morphological and hematological abnormalities such as pancytopenia, macrocytic anaemia and progressive bone marrow failure. Genetic examination, often very complex, includes chromosomal breakage testing and mutational analysis. Case presentation: We present a child with clinical diagnosis of Fanconi anemia. Although morphological abnormalities of skin and bones were present from birth, diagnosis was only suspected at the age of 8. Chromosome breakage test in patient's lymphocytes showed increased level of aberrations (gaps, chromatid breaks, chromosome breaks, radial figures and rearrangements) compared to control. Next generation sequencing revealed presence of two pathogenic variants in FANCA gene, one of which was not previously reported. Conclusions: The article provides additional supportive evidence that compound biallelic mutations of FANCA are associated with Fanconi anemia. It also illustrates the utility of combination of cytogenetic and molecular tests, together with detailed clinical evaluation in providing accurate diagnosis of Fanconi anemia. This report, to the best of our knowledge, describes the first fully diagnosed FA patient in Polish population.

show abstract

Molecular analysis of the most prevalent mutations of the FANCA and FANCC genes in Brazilian patients with Fanconi anaemia

Cited by 5 publications

References 30 publications

Analysis of FANCC gene mutations (IVS4+4A>T, del322G, and R548X)in patients with Fanconi anemia in Pakistan

Analysis of FANCC gene mutations (IVS4+4A>T, del322G, and R548X)in patients with Fanconi anemia in Pakistan

Características clínicas de pacientes com anemia de Fanconi

Novel FANCA mutation in the first fully-diagnosed patient with Fanconi anemia in Polish population – case report

Contact Info

Product

Resources

About