Founder mutations have been reported in BRCA1 and BCRA2 in different ethnic groups with inherited breast cancer. Testing of targeted mutations in specific populations is important for cancer prevention in mutation carriers. In Sub-Saharan Africa, only a few studies have reported specific founder mutations in inherited breast cancer. The pathogenic variant c.815_824dup of BRCA1 has been reported as the most frequent among African American populations with inherited breast cancer and was supposed to have a West African origin. Recent report from Senegal identified this variant in women with inherited breast cancer at the highest frequency ever reported. The variant was linked to a common haplotype confirming its founder effect in West Africa. In this article, we review the mutation history of c.815_824dup and discuss how it spread out of Africa through the transatlantic slave trade.

This study aimed to investigate GJB2 (MIM: 121011) and GJB6 (MIM: 604418) variants associated with familial non-syndromic hearing impairment (HI) in Senegal. We investigated a total of 129 affected and 143 unaffected individuals from 44 multiplex families by segregating autosomal recessive non-syndromic HI, 9 sporadic HI cases of putative genetic origin, and 148 control individuals without personal or family history of HI. The DNA samples were screened for GJB2 coding-region variants and GJB6-D3S1830 deletions. The mean age at the medical diagnosis of the affected individuals was 2.93 ± 2.53 years [range: 1–15 years]. Consanguinity was present in 40 out of 53 families (75.47%). Variants in GJB2 explained HI in 34.1% (n = 15/44) of multiplex families. A bi-allelic pathogenic variant, GJB2: c.94C>T: p.(Arg32Cys) accounted for 25% (n = 11/44 families) of familial cases, of which 80% (n = 12/15) were consanguineous. Interestingly, the previously reported “Ghanaian” founder variant, GJB2: c.427C>T: p.(Arg143Trp), accounted for 4.5% (n = 2/44 families) of the families investigated. Among the normal controls, the allele frequency of GJB2: c.94C>T and GJB2: c.427C>T was estimated at 1% (2/148 ∗ 2) and 2% (4/148 ∗ 2), respectively. No GJB6-D3S1830 deletion was identified in any of the HI patients. This is the first report of a genetic investigation of HI in Senegal, and suggests that GJB2: c.94C>T: p.(Arg32Cys) and GJB2: c.427C>T: p.(Arg143Trp) should be tested in clinical practice for congenital HI in Senegal.

We recently showed that variants in GJB2 explained Hearing Impairment (HI) in 34.1% (n = 15/44) of multiplex families in Senegal. The present study aimed to use community-based nationwide recruitment to determine the etiologies and the clinical profiles of childhood HI in Senegal. Participants with early onset HI were included after clinical examination, including audiological assessment by pure tone audiometry and/or auditory brainstem response. We investigated a total of 406 participants from 295 families, recruited from 13/14 administrative regions of Senegal. Male/female ratio was 1.33 (232/174). Prelingual HI was the most common type of HI and accounted for 80% (n = 325 individuals). The mean age at medical diagnosis for congenital HI was computed at 3.59 ± 2.27 years. Audiological evaluation showed sensorineural HI as the most frequently observed HI (89.16%; n = 362 individuals). Pedigree analysis suggested autosomal recessive inheritance in 61.2% (63/103) of multiplex families and sporadic cases in 27 families (26.2%; 27/103), with a consanguinity rate estimated at 93% (84/90 families). Genetic factors were likely involved in 52.7% (214/406) of the cases, followed by environmental causes (29.57%; 120/406). In 72 cases (17.73%), the etiology was unknown. Clinically, non-syndromic HI was the most common type of HI (90.6%; n = 194/214 individuals). Among families segregating syndromic cases, type 2 Waardenburg syndrome was the most common (36.3%; 4/11 families). This study revealed putative genetic factors, mostly associated with high consanguinity rate, as the leading causes of early-onset HI in Senegal. The high consanguinity could provide a good opportunity to identify variants in known and novel genes involved in childhood HI.