Fanconi anemia in black African children

Macdougall, Lorna G.; Greeff, Michael; Rosendorff, Jennifer; Bernstein, R

doi:10.1002/ajmg.1320360408

Cited by 18 publications

(15 citation statements)

References 14 publications

(3 reference statements)

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“…The true incidence of FA would be higher, since this mutation accounts for 80% of FA alleles in the population and is therefore likely to be about 10-fold higher than that reported from clinical ascertainment of FA in black school children and estimates of population size from a population census. 5 We also investigated the clinical phenotype of black South African patients homozygous for the FANCG deletion. Detailed clinical information was available from 20 patients, and this was compared to data from 20 European FA-G patients and from all 245 European FA patients described previously.…”

Section: Resultsmentioning

confidence: 99%

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A common Fanconi anemia mutation in black populations of sub-Saharan Africa

Morgan

Essop

Demuth

et al. 2005

Blood

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Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer. We report that a deletion mutation in the FANCG gene (c.637_643delTACCGCC) was present in 82% of FA patients in the black populations of Southern Africa. These patients originated from South Africa, Swaziland, Mozambique, and Malawi. The mutation was found on the same haplotype and was present in 1% of controls from the black South African population. These data indicate that the birth incidence of FA in this population is higher than 1 in 40 000, which is much higher than previously supposed, and suggest that the FANCG deletion is an ancient founder mutation in Bantu-speaking populations of sub-Saharan Africa.

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Section: Resultsmentioning

confidence: 99%

“…4 Clinical studies indicated that FA is rare in black South Africans, with a homozygote prevalence of 1 in 476 000. 5 We investigated the molecular basis of FA in this population to inform future patient management strategies.…”

Section: Fancc Fancd1/brca2 Fancd2 Fance Fancf Fancg Fanci Fanmentioning

confidence: 99%

A common Fanconi anemia mutation in black populations of sub-Saharan Africa

Morgan

Essop

Demuth

et al. 2005

Blood

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“…9 Notwithstanding advances in standards of care, the health-care system in South Africa remains underdeveloped and is largely based on semi-urban and rural primary health-care clinics that are predominantly staffed by nurses. Despite the severity of FA, it has previously been postulated that only a small percentage of affected patients are recognized in these local and regional health-care institutions and referred for tertiary management 9,10 although the reasons for this remain unclear.…”

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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“…[14] Evidence further suggested that the clinical manifestations of FA in this population were similar to those in other ethnic groups. [12] This finding was further confirmed in a comparative study of FA in various SA ethnic groups. [13] Newer studies in black patients with known FANCG mutations have identified both similarities and differences with regards to the phenotypic manifestations of FA.…”

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confidence: 62%

“…Initial reports seemed to suggest FA in black individuals was very rare. [12] However, Macdougall et al [13] estimated the incidence of FA in this population as 1/476 000 in a case-based ascertainment study. More recently, gene frequency studies have shown that FA has a carrier frequency of 1/100 in black SA patients and therefore an expected birth incidence of 1/40 000.…”

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confidence: 88%

Fanconi anaemia in black South African patients heterozygous for the FANCG c.637-643delTACCGCC founder mutation

et al. 2013

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Background. Fanconi anaemia (FA) is an autosomal recessive, genetically heterogeneous disorder, characterised by interstrand crosslinkinduced chromosome breaks, congenital abnormalities and predisposition to malignancies. It has a prevalence of about 1/40 000 in black South Africans (SAs). A founder mutation in the FANCG gene occurs in the homozygous state in 77.5% of southern African blacks. Objective. To locate additional pathogenic mutations in the FANCG gene of black FA patients who were heterozygous for the founder mutation. Methods. Further mutation analysis of the FANCG gene was undertaken in 7 patients clinically suspected of having FA. The parents of two of the patients were tested for the presence of the founder mutation to determine true heterozygosity in the patients. To clarify whether or not previously unreported variants were pathogenic, 58 random black SA individuals were screened. Results. Three novel single base pair deletions, resulting in frameshift mutations (c.247delA, c.179delT and c.899delT) were identified in 3/7 patients. A fourth patient was found to have a single base substitution resulting in a splice site mutation (c.1636+1G>A). The remaining three patients were not found to harbour any pathogenic mutations. Two non-pathogenic variants were also identified among the seven patients. Conclusion. The results of this small sample suggest that a second common mutation in the FANCG gene is unlikely in this population. However, FANCG sequencing should be performed on patients heterozygous for the common founder mutation to attempt to confirm their diagnosis.

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Fanconi anemia in black African children

Cited by 18 publications

References 14 publications

A common Fanconi anemia mutation in black populations of sub-Saharan Africa

A common Fanconi anemia mutation in black populations of sub-Saharan Africa

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

Fanconi anaemia in black South African patients heterozygous for the FANCG c.637-643delTACCGCC founder mutation

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