title: High-resolution array-CGH in patients with oculocutaneous albinism identifies new deletions of the TYR, OCA2, and SLC45A2 genes and a complex rearrangement of the OCA2 gene.
abstract: Oculocutaneous albinism (OCA) is caused by mutations in six different genes, and their molecular diagnosis encompasses the search for point mutations and intragenic rearrangements. Here, we used high-resolution array-comparative genome hybridization (CGH) to search for rearrangements across exons, introns and regulatory sequences of four OCA genes: TYR, OCA2, TYRP1, and SLC45A2. We identified a total of ten new deletions in TYR, OCA2, and SLC45A2. A complex rearrangement of OCA2 was found in two unrelated patients. Whole-genome sequencing showed deletion of a 184-kb fragment (identical to a deletion previously found in Polish patients), whereby a large portion of the deleted sequence was re-inserted after severe reshuffling into intron 1 of OCA2. The high-resolution array-CGH presented here is a powerful tool to detect gene rearrangements. Finally, we review all known deletions of the OCA1-4 genes reported so far in the literature and show that deletions or duplications account for 5.6% of all mutations identified in the OCA1-4 genes.
authors.affiliation: Service de Génétique Médicale, CHU de Bordeaux, Bordeaux, France; Maladies Rares: Génétique et Métabolisme (MRGM) EA4576, Univ. Bordeaux, Bordeaux, France.
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: Audrey
authors.initials: A
authors.lastname: Gros
authors.forename: Jérome
authors.initials: J
authors.lastname: Toutain
authors.forename: Claudio
authors.initials: C
authors.lastname: Plaisant
authors.forename: Delphine
authors.initials: D
authors.lastname: Simon
authors.forename: Stéphane
authors.initials: S
authors.lastname: François
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gilbert-Dussardier
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Benoit
authors.initials: B
authors.lastname: Arveiler
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D055028:Comparative Genomic Hybridization; D055106:Genome-Wide Association Study; D026901:Membrane Transport Proteins / Q000235:genetics*; D014442:Monophenol Monooxygenase / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C510061:SLC45A2 protein, human; D014442:Monophenol Monooxygenase
keywords: OCA genes; deletions; high-resolution array-CGH; oculocutaneous albinism; rearrangements; whole-genome sequencing