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DNA Variations in Oculocutaneous Albinism: An Updated Mutation List and Current Outstanding Issues in Molecular Diagnostics
Author(s) -
Simeonov Dimitre R.,
Wang Xinjing,
Wang Chen,
Sergeev Yuri,
Dolinska Monika,
Bower Matthew,
Fischer Roxanne,
Winer David,
Dubrovsky Genia,
Balog Joan Z.,
Huizing Marjan,
Hart Rachel,
Zein Wadih M.,
Gahl William A.,
Brooks Brian P.,
Adams David R.
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22315
Subject(s) - oculocutaneous albinism , albinism , biology , genetics , sanger sequencing , mutation , in silico , gene
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 SLC45 A 2 ( 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 N atural H istory S tudy and eight from a prior study at the U niversity of M innesota. 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 S anger sequencing. Finally, we review the TYR p. R 402 Q temperature‐sensitive variant and confirm its association with cases of albinism with only one identifiable TYR mutation.