Fanconi anaemia

Tischkowitz, Marc

doi:10.1136/jmg.40.1.1

Cited by 260 publications

(209 citation statements)

References 133 publications

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“…In addition, several different mutations have been identified in each one of these genes, which makes the disease even more genetically heterogeneous. The genes BRCA1 (OMIM 113705) (1) and BRCA2 (OMIM 600185) (1) are also associated with the abnormal DNA repair pathway in FA, and it has been recently found that FANCD1 and BRCA2 genes are actually the same gene (4,5,7,11) . Among the complementation groups, the most often mentioned is A (FANCA), reported in 57 to 65% of the cases (11) .…”

Section: Discussionmentioning

confidence: 99%

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Características clínicas de pacientes com anemia de Fanconi

Zen

Moraes

Rosa

et al. 2011

Rev. paul. pediatr.

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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.

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Section: Discussionmentioning

confidence: 99%

“…This syndrome was first described in 1927 by Swiss pediatrician Guido Fanconi. The disease was characterized as a rare form of familial aplastic anemia affecting three siblings with short stature, hypogonadism, and skin disorders (2)(3)(4)(5)(6) .…”

Section: Introductionmentioning

confidence: 99%

Características clínicas de pacientes com anemia de Fanconi

Zen

Moraes

Rosa

et al. 2011

Rev. paul. pediatr.

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“…4 Bone marrow failure remains, however, the hallmark of the disease, with initial pancytopenia and progression to aplastic anemia, acute myeloid leukemia, or myelodysplastic syndrome. 5 A predisposition to solid tumors of the head, neck, liver, esophagus, and female genital tract is also well described and has become more prevalent in developed countries, as the treatment for the hematological complications of the condition has improved. Bone marrow transplantation now provides the possibility of cure for the hematological complications of the condition.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic consequences in black South African Fanconi anemia patients homozygous for a founder mutation

Feben

Kromberg

Wainwright

et al. 2014

Genetics in Medicine

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Purpose: Fanconi anemia is a genotypically and phenotypically heterogeneous condition, characterized microscopically by chromosomal instability and breakage. Affected individuals manifest growth restriction and congenital physical abnormalities; most progress to hematological disease including bone marrow aplasia. Black South African Fanconi anemia patients share a common causative founder mutation in the Fanconi G gene in 80% of cases (637_643delTACC-GCC). The aim of this study was to investigate the genotype-physical phenotype correlation in a cohort of individuals homozygous for this mutation.Methods: Thirty-five black patients were recruited from tertiary level hematology/oncology clinics in South Africa. Participants were subjected to a comprehensive clinical examination, documenting growth, congenital anomalies, and phenotypic variability.Results: Descriptive statistical analysis showed significant growth abnormalities in many patients and a high frequency (97%) of skin pigmentary anomalies. Subtle anomalies of the eyes, ears, and hands occurred frequently (≥70%). Apart from malformations of the kidney (in 37%) and gastrointestinal tract (in 8.5%), congenital anomalies of other systems including the cardiovascular and central nervous systems, genitalia, and vertebrae were infrequent (<5%). Conclusion:The diagnosis of Fanconi anemia in black South African patients before the onset of hematological symptoms remains a clinical challenge, with the physical phenotype unlikely to be recognized by those without dysmorphology expertise.Genet Med advance online publication 26 December 2013

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“…[1][2][3] Fifteen genes, defining 15 complementation groups, have been shown to be involved in FA. 4 One of them, FANCD1, corresponds to the BRCA2 gene, one of the main genes involved in autosomal dominant predisposition to breast and ovarian cancers.…”

Section: Introductionmentioning

confidence: 99%

Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene

et al. 2013

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Fanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and a missense mutation (c.7802A4G, p.Tyr2601Cys). The diagnosis of FA was confirmed by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR analysis revealed that the c.7802A4G BRCA2 variation was in fact a splicing mutation that creates an aberrant splicing donor site and results partly into an aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The atypical FA phenotype observed within this family was probably explained by the residual amount of BRCA2 with the point mutation c.7802A4G in the patients harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in a single family, it suggests that CRCs may be part of the tumour spectrum associated with FANCD1/BRCA2 biallelic mutations and that the presence of such mutations should be considered in families with CRCs, even in the absence of cardinal features of FA.

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Fanconi anaemia

Cited by 260 publications

References 133 publications

Características clínicas de pacientes com anemia de Fanconi

Características clínicas de pacientes com anemia de Fanconi

Phenotypic consequences in black South African Fanconi anemia patients homozygous for a founder mutation

Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene

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