title: DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics.
abstract: Oculocutaneous albinism (OCA) is a rare genetic disorder of melanin synthesis that results in hypopigmented hair, skin, and eyes. There are four types of OCA caused by mutations in TYR (OCA-1), OCA2 (OCA-2), TYRP1 (OCA-3), or SLC45A2 (OCA-4). Here we report 22 novel mutations in the OCA genes; 14 from a cohort of 61 patients seen as part of the NIH OCA Natural History Study and eight from a prior study at the University of Minnesota. We also include a comprehensive list of almost 600 previously reported OCA mutations along with ethnicity information, carrier frequencies, and in silico pathogenicity predictions as a supplement. In addition to discussing the clinical and molecular features of OCA, we address the cases of apparent missing heritability. In our cohort, 26% of patients did not have two mutations in a single OCA gene. We demonstrate the utility of multiple detection methods to reveal mutations missed by Sanger sequencing. Finally, we review the TYR p.R402Q temperature-sensitive variant and confirm its association with cases of albinism with only one identifiable TYR mutation.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dimitre R
authors.initials: DR
authors.lastname: Simeonov
authors.forename: Xinjing
authors.initials: X
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sergeev
authors.forename: Monika
authors.initials: M
authors.lastname: Dolinska
authors.forename: Matthew
authors.initials: M
authors.lastname: Bower
authors.forename: Roxanne
authors.initials: R
authors.lastname: Fischer
authors.forename: David
authors.initials: D
authors.lastname: Winer
authors.forename: Genia
authors.initials: G
authors.lastname: Dubrovsky
authors.forename: Joan Z
authors.initials: JZ
authors.lastname: Balog
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: Rachel
authors.initials: R
authors.lastname: Hart
authors.forename: Wadih M
authors.initials: WM
authors.lastname: Zein
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.forename: David R
authors.initials: DR
authors.lastname: Adams
mesh_terms: D016115:Albinism, Oculocutaneous / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D015995:Prevalence; D013329:Structure-Activity Relationship
chemical_list: D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C510061:SLC45A2 protein, human; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase