title: 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.
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Faculté de Médecine, Université de la Méditerranée Aix-Marseille II, 27 Boulevard Jean Moulin, 13385, Marseille, Cedex 5, France. robert.aquaron@medecine.univ-mrs.fr.
authors.forename: Robert
authors.initials: R
authors.lastname: Aquaron
authors.affiliation: Biochimie hormonale et Génétique, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Nadem
authors.initials: N
authors.lastname: Soufir
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de la Conception, Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bergé-Lefranc
authors.affiliation: Faculté de Médecine, Centre d'Enseignement et de Recherche en Génétique Médicale, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
authors.affiliation: Laboratoire Ecologie, Systématique et Evolution, UMR CNRS/UPS/ENGREF 8079, Université Paris Sud, Orsay, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Austerlitz
authors.affiliation: Biochimie hormonale et Génétique, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics* / Q000378:metabolism; D000755:Anemia, Sickle Cell / Q000235:genetics*; D002163:Cameroon; D016022:Case-Control Studies; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D005914:Globins