X-linked inheritance of Fanconi anemia complementation group B

Meetei, Amom Ruhikanta; Levitus, Marieke; Xue, Yutong; Medhurst, Annette L.; Zwaan, Michel; Chen, Ling; Rooimans, Martin A.; Bier, Patrick; Hoatlin, Maureen E.; Pals, Gerard; Winter, Johan P. de; Wang, Weidong; Joenje, Hans

doi:10.1038/ng1458

Cited by 266 publications

(237 citation statements)

References 24 publications

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“…The majority of the population will have two functional copies of their FA genes, and would therefore require somatic mutation of both alleles of the same FA gene to inactivate the pathway. An important exception to this is the FANCB gene which is located on the X chromosome (Meetei et al, 2004). All males are effectively FA carriers, and only one somatic mutation will therefore be required for loss of function of the FA pathway, and in females one copy would be subject to Xinactivation.…”

Section: Discussionmentioning

confidence: 99%

“…The disorder generally presents as aplastic anaemia between the ages of 5-10 years, but the diagnosis may be made much earlier if characteristic developmental abnormalities are present or if there is a family history, or much later if the haematological symptoms are very mild. FA is inherited mainly as an autosomal recessive trait, but is genetically heterogeneous, with multiple complementation groups that include an X-linked form (Meetei et al, 2004). It is a rare disease with an incidence of 1 in 200 000-400 000 live births (Joenje and Patel, 2001), and a heterozygote frequency of around 1 in 250.…”

Section: The Fanconi Anaemia Syndromementioning

confidence: 99%

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Fanconi anaemia genes and susceptibility to cancer

2006

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Fanconi anaemia (FA) is a rare recessive disorder associated with chromosomal fragility, aplastic anaemia, congenital abnormalities and a high risk of cancer, including acute myeloid leukaemia and squamous cell carcinomas. The identification of 11 different FA genes has revealed a complex web of interacting proteins that are involved in the recognition or repair of DNA interstrand crosslinks and perhaps other forms of DNA damage. Bi-allelic mutations in BRCA2 are associated with a rare and highly cancer-prone form of FA, and the DNA helicase BRIP1 (formerly BACH1) is mutated in FA group J. There is little convincing evidence that FA heterozygotes are at increased risk of cancer, but larger studies are needed to address the possibility of modest risk effects. Somatic inactivation of the FA pathway by mutation or epigenetic silencing has been observed in several different types of sporadic cancer, and this may have important implications for targeted chemotherapy. Inhibition of this pathway represents a possible route to sensitization of tumours to DNA crosslinking drugs such as cisplatin.

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Section: Discussionmentioning

confidence: 99%

Section: The Fanconi Anaemia Syndromementioning

confidence: 99%

Fanconi anaemia genes and susceptibility to cancer

2006

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“…Absence of the FANCA protein shortens the halflife of the FANCG protein (Garcia-Higuera et al 2000). Molecular studies support interactions between FANCG and FANCF (Garcia-Higuera et al 2000), between FANCE and FANCC (Pace et al 2002;Taniguchi and D'Andrea 2002), and between FANCB and FANCL subunits (Meetei et al 2004). The FANCE protein is required for the efficient transport of the FANCC protein to the nucleus (Pace et al 2002;Taniguchi and D'Andrea 2002).…”

Section: The Structure Of the Fa Complexmentioning

confidence: 95%

The Fanconi Anemia/BRCA pathway: new faces in the crowd

Kennedy¹,

D’Andrea²

2005

Genes Dev.

362

345

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Over the past few years, study of the rare inherited chromosome instability disorder, Fanconi Anemia (FA), has uncovered a novel DNA damage response pathway. Through the cooperation of multiple proteins, this pathway regulates a complicated cellular response to DNA cross-linking agents and other genotoxic stresses. In this article we review recent data identifying new components of the FA pathway that implicate it in several aspects of the DNA damage response, including the direct processing of DNA, translesion synthesis, homologous recombination, and cell cycle regulation. We also discuss new findings that explain how the FA pathway is regulated through the processes of ubiquitination and deubiquitination. We then consider the clinical implications of our current understanding of the FA pathway, particularly in the development and treatment of malignancy in heterozygous carriers of FA mutations or in patients with sporadic cancers. We consider how recent studies of p53-mediated apoptosis and loss of p53 function in models of FA may help explain the clinical features of the disease and finally present a hypothesis to account for the specificity of the FA pathway in the response to DNA cross-links.

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“…1,2 It is both genotypically and phenotypically heterogeneous and is a disorder that affects individuals of diverse ethnic origin.…”

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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X-linked inheritance of Fanconi anemia complementation group B

Cited by 266 publications

References 24 publications

Fanconi anaemia genes and susceptibility to cancer

Fanconi anaemia genes and susceptibility to cancer

The Fanconi Anemia/BRCA pathway: new faces in the crowd

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

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