Academic Journal
Evidence that the Ser192Tyr/Arg402Gln in cis Tyrosinase gene haplotype is a disease-causing allele in oculocutaneous albinism type 1B (OCA1B)
| العنوان: | Evidence that the Ser192Tyr/Arg402Gln in cis Tyrosinase gene haplotype is a disease-causing allele in oculocutaneous albinism type 1B (OCA1B) |
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| المؤلفون: | Lin, S., Sanchez-Bretaño, A., Leslie, J. S., Williams, K. B., Lee, H., Thomas, N. S., Callaway, J., Deline, J., Ratnayaka, J. A., Baralle, D., Schmitt, M. A., Norman, C. S., Hammond, S., Harlalka, G. V., Ennis, S., Cross, H. E., Wenger, O., Crosby, A. H., Baple, E. L., Self, J. E. |
| بيانات النشر: | PubMed Central |
| سنة النشر: | 2022 |
| المجموعة: | RD&E Research Repository (Royal Devon and Exeter NHS Foundation Trust) |
| الوصف: | Oculocutaneous albinism type 1 (OCA1) is caused by pathogenic variants in the TYR (tyrosinase) gene which encodes the critical and rate-limiting enzyme in melanin synthesis. It is the most common OCA subtype found in Caucasians, accounting for ~50% of cases worldwide. The apparent 'missing heritability' in OCA is well described, with ~25-30% of clinically diagnosed individuals lacking two clearly pathogenic variants. Here we undertook empowered genetic studies in an extensive multigenerational Amish family, alongside a review of previously published literature, a retrospective analysis of in-house datasets, and tyrosinase activity studies. Together this provides irrefutable evidence of the pathogenicity of two common TYR variants, p.(Ser192Tyr) and p.(Arg402Gln) when inherited in cis alongside a pathogenic TYR variant in trans. We also show that homozygosity for the p.(Ser192Tyr)/p.(Arg402Gln) TYR haplotype results in a very mild, but fully penetrant, albinism phenotype. Together these data underscore the importance of including the TYR p.(Ser192Tyr)/p.(Arg402Gln) in cis haplotype as a pathogenic allele causative of OCA, which would likely increase molecular diagnoses in this missing heritability albinism cohort by 25-50%. ; The article is available via Open Access. Click on the 'Additional link' above to access the full-text. ; Published version |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://doi.org/10.1038/s41525-021-00275-9; NPJ Genom Med. 2022 Jan 13;7(1):2. doi:10.1038/s41525-021-00275-9.; https://rde.dspace-express.com/handle/11287/622393; NPJ genomic medicine; PMC8758782 |
| DOI: | 10.1038/s41525-021-00275-9 |
| الاتاحة: | https://doi.org/10.1038/s41525-021-00275-9 https://rde.dspace-express.com/handle/11287/622393 |
| Rights: | © 2022. The Author(s). |
| رقم الانضمام: | edsbas.E3F58061 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41525-021-00275-9 |
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