Fanconi anaemia in South Africa: Past, present and future

Feben, Candice; Wainstein, Tasha; Kromberg, J. G. R.; Essop, Fahmida; Krause, Amanda

doi:10.7196/samj.2018.v108i5.13004

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…It includes hypoplastic gonads, hypogenitalia, undescended testes, micropenis, cryptorchidism, hypospadias, and hypo-/azoospermia with infertility. Females may also have underdeveloped genitalia and malpositioned uterus with small ovaries [13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Homozygous Mutation in the FANCD2 Gene Observed in a Saudi Male Infant with Severe Ambiguous Genitalia

Jabri

Naim

Dossari

2021

Case Reports in Endocrinology

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Fanconi anemia (FA) is a rare autosomal recessive inherited disease caused by gene mutations that are primarily involved in the response to or repair of DNA damage. FA characterizes by multiple congenital abnormalities and malformations including growth retardation, renal agenesis, absence of radial bones and thumbs as well, progressive bone marrow failure, irregular skin pigmentation patterns, and increased susceptibility to cancer. FANCD2 gene mutation is believed to be one of the causative mutations in Fanconi anemia, and despite many case reports that link the FANC gene mutation to multiple congenital anomalies and disease, there is no case report found to link it with genitalia abnormalities. In our paper, we report a male Saudi infant who presented to the endocrine clinic at the age of 9 months with severe ambiguous genitalia and found that he carries a homozygous variant mutation in the FANCD2 gene and we face a challenge to treat this patient since there was no previous similar case.

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Section: Discussionmentioning

confidence: 99%

Homozygous Mutation in the FANCD2 Gene Observed in a Saudi Male Infant with Severe Ambiguous Genitalia

Jabri

Naim

Dossari

2021

Case Reports in Endocrinology

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“…There is concern that large discrepancies exist between the numbers of observed and expected cases of FA, indicating that many cases are unrecognized or undiagnosed. Data suggest that only 1 in 15 cases of FA will have molecular confirmation of their diagnosis in South Africa (31). The reasons for this remain unclear.…”

Section: Fanconi Anemiamentioning

confidence: 99%

Common and Founder Mutations for Monogenic Traits in Sub-Saharan African Populations

Krause

Seymour

Ramsay

2018

Annu. Rev. Genom. Hum. Genet.

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This review highlights molecular genetic studies of monogenic traits where common pathogenic mutations occur in black families from sub-Saharan Africa. Examples of founder mutations have been identified for oculocutaneous albinism, cystic fibrosis, Fanconi anemia, and Gaucher disease. Although there are few studies from Africa, some of the mutations traverse populations across the continent, and they are almost all different from the common mutations observed in non-African populations. Myotonic dystrophy is curiously absent among Africans, and nonsyndromic deafness does not arise from mutations in GJB2 and GJB7. Locus heterogeneity is present for Huntington disease, with two common triplet expansion loci in Africa, HTT and JPH3. These findings have important clinical consequences for diagnosis, treatment, and genetic counseling in affected families. We currently have just a glimpse of the molecular etiology of monogenic diseases in sub-Saharan Africa, a proverbial "ears of the hippo" situation.

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“…Although FA is thought to be a rare disorder, the prevalence in certain South African population groups, such as the Afrikaner and Black populations, has been found to be much higher (Tipping et al, 2001). The term "Black" has been used to describe individuals deriving from sub-Saharan Bantuspeaking indigenous ancestry groups (Feben, Wainstein, Kromberg, Essop, & Krause, 2018). Morgan et al (2005) proposed that the birth incidence of FA in the Black South African population is higher than 1 in 40,000 based on carrier frequency data obtained from gene frequency studies.…”

Section: Introductionmentioning

confidence: 99%

Endocrine profiling in patients with Fanconi anemia, homozygous for a FANCG founder mutation

Dillon

Feben

Segal

et al. 2020

Molec Gen & Gen Med

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Background Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highlighted that these abnormalities are widespread among children and adults with FA. To date there has been no systematic study that has evaluated the endocrine abnormalities in a cohort of patients with FA, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG . The objectives of the study were to evaluate endocrine gland function in patients with FA of a single FA genotype, and to determine the frequency and nature of endocrine abnormalities in this group. Methods Cross‐sectional, descriptive study of 24 South African patients of African ancestry with FA (homozygous for a FANCG founder mutation). Outcomes measured included growth, pubertal status, growth hormone axis screening, thyroid gland function, glucose and insulin metabolism and bone age (BA). Results Endocrine dysfunction was present in 70.8% (17 of 24), including abnormal insulin‐like growth factor 1 (IGF‐1)/insulin‐like growth factor‐binding protein 3 (IGFBP‐3) in 25.0% (6 of 24), insulin resistance in 41.7% (10 of 24), abnormal thyroid function in 16.7% (4 of 24) and short stature in 45.8% (11 of 24). No abnormalities of glucose metabolism were identified. Abnormal pubertal status was seen in three males (12.5%). Abnormal BAs were present in 34.8% (8 of 23). Conclusion Endocrine abnormalities occur at a high frequency in patients with FA, homozygous for a FANCG founder mutation, similar to other FA cohorts. Our data are specific to FA patients with a single genotype, and therefore provide the first genotype‐phenotype information on endocrine abnormalities in South African patients, homozygous for a FANCG founder mutation. Recommendations regarding endocrine screening in this patient subgroup are made, including, but not limited to, baseline testing of thyroid function, fasted insulin and glucose, and IGF‐1 and IGFBP‐3.

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Fanconi anaemia in South Africa: Past, present and future

Cited by 5 publications

References 41 publications

Homozygous Mutation in the FANCD2 Gene Observed in a Saudi Male Infant with Severe Ambiguous Genitalia

Homozygous Mutation in the FANCD2 Gene Observed in a Saudi Male Infant with Severe Ambiguous Genitalia

Common and Founder Mutations for Monogenic Traits in Sub-Saharan African Populations

Endocrine profiling in patients with Fanconi anemia, homozygous for a FANCG founder mutation

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