Young T L, Ronan S M, Alvear A B, Wildenberg S C, Oetting W S, Atwood L D, Wilkin D J, King R A
Department of Opthalmology, Division of Epidemiology, University of Minnesota, Minneapolis, MN, USA.
Am J Hum Genet. 1998 Nov;63(5):1419-24. doi: 10.1086/302111.
Myopia, or nearsightedness, is the most common eye disorder worldwide. "Pathologic" high myopia, or myopia of <=-6.00 diopters, predisposes individuals to retinal detachment, macular degeneration, cataract, or glaucoma. A locus for autosomal dominant pathologic high myopia has been mapped to 18p11.31. We now report significant linkage of high myopia to a second locus at the 12q21-23 region in a large German/Italian family. The family had no clinical evidence of connective-tissue abnormalities or glaucoma. The average age at diagnosis of myopia was 5.9 years. The average spherical-component refractive error for the affected individuals was -9.47 diopters. Markers flanking or intragenic to the genes for the 18p locus, Stickler syndromes type I and II (12q13.1-q13.3 and 6p21.3), Marfan syndrome (15q21.1), and juvenile glaucoma (chromosome 1q21-q31) showed no linkage to the myopia in this family. The maximum LOD score with two-point linkage analysis in this pedigree was 3.85 at a recombination fraction of .0010, for markers D12S1706 and D12S327. Recombination events identified markers D12S1684 and D12S1605 as flanking markers that define a 30.1-cM interval on chromosome 12q21-23, for the second myopia gene. These results confirm genetic heterogeneity of myopia. The identification of this gene may provide insight into the pathophysiology of myopia and eye development.
近视，即近视眼，是全球最常见的眼部疾病。“病理性”高度近视，即屈光度≤ -6.00的近视，会使个体易患视网膜脱离、黄斑变性、白内障或青光眼。常染色体显性病理性高度近视的一个基因座已被定位到18p11.31。我们现在报告，在一个庞大的德裔/意裔家族中，高度近视与位于12q21 - 23区域的第二个基因座存在显著连锁关系。该家族没有结缔组织异常或青光眼的临床证据。近视诊断的平均年龄为5.9岁。受影响个体的平均球镜成分屈光不正为 -9.47屈光度。位于18p基因座、I型和II型Stickler综合征（12q13.1 - q13.3和6p21.3）、马凡综合征（15q21.1）以及青少年青光眼（染色体1q21 - q31）相关基因两侧或基因内的标记物，在这个家族中与近视均无连锁关系。在这个家系中，两点连锁分析在重组率为0.0010时，与标记物D12S1706和D12S327的最大对数优势分数为3.85。重组事件确定标记物D12S1684和D12S1605为侧翼标记物，它们界定了12q21 - 23染色体上第二个近视基因的一个30.1厘摩区间。这些结果证实了近视的遗传异质性。该基因的鉴定可能为近视的病理生理学和眼睛发育提供深入见解。
