title: High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2.
abstract: 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.
authors: The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer-Sheva Israel.
authors: Shikma
authors: S
authors: Mordechai
authors: Libe
authors: L
authors: Gradstein
authors: Annika
authors: A
authors: Pasanen
authors: Rivka
authors: R
authors: Ofir
authors: Khalil
authors: K
authors: El Amour
authors: Jaime
authors: J
authors: Levy
authors: Nadav
authors: N
authors: Belfair
authors: Tova
authors: T
authors: Lifshitz
authors: Sara
authors: S
authors: Joshua
authors: Ginat
authors: G
authors: Narkis
authors: Khalil
authors: K
authors: Elbedour
authors: Johanna
authors: J
authors: Myllyharju
authors: Ohad S
authors: OS
authors: Birk
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D040461:Gene Components; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009216:Myopia / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D011393:Procollagen-Proline Dioxygenase; C568061:P3H2 protein, human