A pathogenic haplotype, common in Europeans, causes autosomal recessive albinism and uncovers missing heritability in OCA1

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review



  • Author: Grønskov, Karen

    Copenhagen University Hospital, Denmark

  • Author: Jespersgaard, Cathrine

    Copenhagen University Hospital, Denmark

  • Author: Bruun, Gitte Hoffmann

    University of Southern Denmark, Denmark

  • Author: Harris, Pernille

    Department of Chemistry, Technical University of Denmark, Denmark

  • Author: Brøndum-Nielsen, Karen

    Copenhagen University Hospital, Denmark

  • Author: Andresen, Brage S.

    University of Southern Denmark, Denmark

  • Author: Rosenberg, Thomas

    Copenhagen University Hospital, Denmark

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Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. Six genes are associated with autosomal recessive OCA (TYR, OCA2, TYRP1, SLC45A2, SLC24A5 and LRMDA), and one gene, GPR143, is associated with X-linked ocular albinism (OA). Molecular genetic analysis provides a genetic diagnosis in approximately 60% of individuals with clinical OA/OCA. A considerably number of the remaining 40% are heterozygous for a causative sequence variation in TYR. To identify missing causative sequence variants in these, we used a NGS based approach, genotyping and segregation analysis. We report two putative pathogenic haplotypes which only differ by two extremely rare SNVs, indicating that the haplotypes have a common derivation. Both haplotypes segregate consistent with an autosomal recessive inheritance pattern and include the allele p.S192Y-p.R402Q. An explanation for the pathogenicity of the haplotypes could be the combination of p.S192Y and p.R402Q. Homozygosity for the pathogenic haplotypes causes a partial albinism phenotype. In our cohort, 15% of affected individuals had a molecular genetic diagnosis involving the pathogenic haplotype. Consequently, the prevalence of albinism seems to be substantially underestimated, and children with unexplained bilateral subnormal vision and/or nystagmus should be analysed clinically and molecularly for albinism.
Original languageEnglish
Article number645
JournalScientific Reports
Issue number1
Number of pages7
Publication statusPublished - 2019
CitationsWeb of Science® Times Cited: No match on DOI

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