Oculocutaneous albinism type 2 (OCA2) with homozygous 2.7-kb deletion of the P gene and sickle cell disease in a Cameroonian family. Identification of a common TAG haplotype in the mutated P gene

Abstract

In this study, we report on a Cameroonian family from the Ewondo ethnic group, presenting with three oculocutaneous albinism type 2 (OCA2) patients homozygous for the 2.7-kb deletion of the P gene. In one of these patients OCA2 was associated with sickle cell anaemia and in two with the sickle cell trait. We took this opportunity to determine single nucleotide polymorphism (SNP) haplotypes within the P gene in this family in comparison with a group of 53 OCA2 patients homozygous for the same mutation and with a matched unrelated full-coloured control group of 49 subjects, originating from seven different ethnic groups of Southern Cameroon including Ewondo. A combination of five exonic and intronic SNPs in the OCA2 gene was genotyped by sequencing PCR products. We found 3 different haplotypes (TAGCT, TAGTT and TAGCC with frequencies of 0.66, 0.28 and 0.06, respectively) associated with the mutation in the 53 OCA2 patients, while 11 different haplotypes were observed in the control group. These observations suggest that the mutation appeared on the relatively frequent haplotype TAGCT, and that the two other haplotypes are derived from two independent recombination events. These haplotypic data, associated with a value of 1/ 15,000 for the prevalence of the 2.7-kb mutation, a present effective population size of 10,000,000 for Cameroon and a recombination rate of 0.0031, allowed us to estimate that this mutation originated 4,100-5,645 years ago.

Dermatological and Epidemiological Profiles of Patients with Albinism in São Paulo, Brazil, between 2010 and 2017: A Cross-Sectional Study

“…Consanguinity was frequent in our group, with 26% of patients in consanguineous families, which is similar to that in Africa [23][24][25] and higher than in European countries, that is, 5-6% [26]. Contrary to our results, another study performed in Bahia, Brazil, reported inbreeding rates similar to those in Europe, with a prevalence of 7.5% [19].…”

Albinism in Europe

“…22 Oculocutaneous albinism type 2 is the commonest OCA in Africa and some mutations in the OCA2 locus have a clearly defined African origin. [23][24][25] However, due to the regular and historic immigration from Africa to Europe, OCA2 cases are not rare among Europeans, and, as such, OCA2 mutations are routinely detected in genetic studies on albinism conducted in European countries, although logically, with lower prevalence, as compared to Africa. [14][15][16] Oculocutaneous albinism type 3, associated with recessive mutations in the TYRP1 gene, is the less frequent type of OCA.…”

“…Eye abnormalities, the most important and handicapping traits for persons with albinism (besides the obvious hypopigmentation), include fovea hypoplasia, reduced pigmentation of retinal pigment epithelium cells, photoreceptor rod cell deficit, misrouting of the optic nerves at the chiasm, reduced pigmentation in the iris, photophobia and nystagmus . Several studies suggest that all known forms of albinism affect 1:17 000 newborns in Western societies, mostly North America and Europe, although frequencies ranging from 1:10 000–20 000 have been also reported and other prevalences apply in Asia . In some countries in Africa, due to consanguinity issues, the prevalence of albinism can be much higher …”

Increasing the complexity: new genes and new types of albinism

“…The prevalence of all known forms of albinism in the best-studied Western populations, mostly in North America and Europe, appears to be 1:17 000 newborns (within a range of 1:10 000-20 000) (Gargiulo et al, 2011;Grønskov et al, 2007Grønskov et al, , 2009Hutton and Spritz, 2008a,b;King and Oetting, 2006;Oetting and King, 1999;Rooryck et al, 2008;Rundshagen et al, 2004;Z€ uhlke et al, 2007). Different frequencies of several types of albinism have been also reported from Asia (Inagaki et al, 2004;Lin et al, 2006;Suzuki and Tomita, 2008;Wei and Li, 2013;Wei et al, 2010Wei et al, , 2011, whereas the highest prevalence is found in some countries in Africa, mostly due to consanguinity issues and founder effects (Aquaron et al, 2007;Cruz-Inigo et al, 2011;Spritz et al, 1995) ( Figure 1).…”