High Myopia Caused by a Mutation in LEPREL1, Encoding Prolyl 3-Hydroxylase 2

作者：Mordechai Shikma; Gradstein Libe; Pasanen Annika; Ofir Riyka; El Amour Khalil; Levy Jaime; Belfair Nadav; Lifshitz Tova; Joshua Sara; Narkis Ginat; Elbedour Khalil; Myllyharju Johanna; Birk Ohad S^*

来源：American Journal of Human Genetics, 2011, 89(3): 438-445.

DOI：10.1016/j.ajhg.2011.08.003

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 theta = 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.

• 出版日期2011-9-9