由 LEPREL1 突变引起的高度近视，该基因编码脯氨酰 3-羟化酶 2。
High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2.
机构信息
The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer-Sheva Israel.
出版信息
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.
常染色体隐性遗传的高度进展性轴性近视在以色列贝都因血缘近亲中被诊断出来。一些受影响的个体也表现出早发性白内障、周边玻璃体视网膜变性的可变表达，以及由于严重视网膜脱离导致的继发性视力丧失。通过全基因组连锁分析，将疾病相关基因定位到染色体 3q28 上的 ∼1.7 Mb 处（标记 D3S1314 处 θ = 0 时最大 LOD 分数为 11.5）。对该定义区域内的六个基因的整个编码区和内含子-外显子边界进行测序，发现 LEPREL1 基因外显子 10 中有一个单一突变（c.1523G>T），该突变编码脯氨酰 3-羟化酶 2（P3H2），这是一种 2-氧戊二酸依赖性双加氧酶，可羟化胶原蛋白。该突变影响 P3H 同工酶内保守的甘氨酸。对在昆虫细胞中表达的野生型和 p.Gly508Val（c.1523G>T）突变重组 P3H2 多肽进行分析表明，该突变导致 P3H2 完全失活。
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