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

Am J Hum Genet. 2011 Sep 9;89(3):438-45. doi: 10.1016/j.ajhg.2011.08.003. Epub 2011 Sep 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Ethnicity / genetics*
  • Female
  • Gene Components
  • Genetic Linkage
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Israel
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics
  • Myopia / genetics*
  • Myopia / pathology
  • Pedigree
  • Procollagen-Proline Dioxygenase / genetics*
  • Sequence Analysis, DNA


  • Procollagen-Proline Dioxygenase
  • P3H2 protein, human