Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Body mass index in young men and risk of inflammatory bowel disease through adult life: A population-based Danish cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Leukocyte telomere length is associated with elevated plasma glucose and HbA1c in young healthy men independent of birth weight

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Collagen turnover profiles in chronic kidney disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypical hand movements

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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
JournalScientific Reports
Volume9
Issue number1
Pages (from-to)645
ISSN2045-2322
DOIs
Publication statusPublished - 24 Jan 2019

ID: 58250615