title: High resolution mapping of OCA2 intragenic rearrangements and identification of a founder effect associated with a deletion in Polish albino patients.
abstract: Oculocutaneous albinism type 2 (OCA2) represents about 30% of OCA worldwide. Using quantitative multiplex fluorescent PCR and very high-resolution array-CGH focussed on the OCA2 gene and surrounding regions in 15q12, we identified new rearrangements. Deletion 1, encompassing exons 3-20, was present in three patients (including one in the homozygous state), and Deletion 2 (exons 1-20) was found in one patient (heterozygous state). The duplication (exons 3-20) was found in one patient in the homozygous state. Using 14 microsatellite markers we determined haplotypes associated with these rearrangements. Deletion 1 was associated with the same haplotype in three patients who were all of Polish origin, which is strongly in favour of a founder effect. Deletion 2 was associated with a distinct haplotype. The homozygous duplication was inherited from the two unrelated parents of the patients on two different haplotypes. Analysis of the sequences around the breakpoints of these rearrangements showed that all occurred within complex arrays of repetitive sequences. The combined use of very high-resolution array-CGH and of microsatellites (including new intragenic ones described here) constitutes a powerful approach for the precise characterization of OCA2 rearrangements, which have been found in more than 20% of OCA2 patients.
authors.affiliation: Laboratoire de Génétique Humaine (EA4137), Université Victor Segalen Bordeaux 2, 146 Rue Léo Saignat, 33076 Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
authors.forename: Fanny
authors.initials: F
authors.lastname: Morice-Picard
authors.forename: Eulalie
authors.initials: E
authors.lastname: Lasseaux
authors.forename: Dorothée
authors.initials: D
authors.lastname: Cailley
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Sabine
authors.initials: S
authors.lastname: Defoort-Dhellemme
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Duban-Bedu
authors.forename: Thomy J L
authors.initials: TJ
authors.lastname: de Ravel
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Benoît
authors.initials: B
authors.lastname: Arveiler
mesh_terms: D016115:Albinism, Oculocutaneous / Q000208:ethnology / Q000235:genetics; D018703:Founder Effect; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D044465:White People / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; C489600:OCA2 protein, human