High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2

Shikma Mordechai, Libe Gradstein, Annika Pasanen, Rivka Ofir, Khalil El Amour, Jaime Levy, Nadav Belfair, Tova Lifshitz, Sara Joshua, Ginat Narkis, Khalil Elbedour, Johanna Myllyharju, Ohad S. Birk

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Autosomal-recessive high-grade axial myopia was diagnosed in Bedouin Israeli consanguineous kindred. Some affected individuals also had variable expressivity of early-onset cataracts, peripheral vitreo-retinal degeneration, and secondary sight loss due to severe retinal detachments. Through genome-wide linkage analysis, the disease-associated gene was mapped to ∼1.7 Mb on chromosome 3q28 (the maximum LOD score was 11.5 at θ = 0 for marker D3S1314). Sequencing of the entire coding regions and intron-exon boundaries of the six genes within the defined locus identified a single mutation (c.1523G>T) in exon 10 of LEPREL1, encoding prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The mutation affects a glycine that is conserved within P3H isozymes. Analysis of wild-type and p.Gly508Val (c.1523G>T) mutant recombinant P3H2 polypeptides expressed in insect cells showed that the mutation led to complete inactivation of P3H2.

Original languageEnglish
Pages (from-to)438-445
Number of pages8
JournalAmerican Journal of Human Genetics
Issue number3
StatePublished - 9 Sep 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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