School of Biomedicine, The University of Manchester, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Invest Ophthalmol Vis Sci. 2011 Oct 4;52(11):7859-65. doi: 10.1167/iovs.10-6581.
Primary open angle glaucoma is the most prevalent type of glaucoma and the leading cause of irreversible blindness worldwide. The genetic basis is poorly understood. Of 14 loci associated with this disease, only two genes have been identified, accounting for approximately 4% of cases. The authors investigated the genetic cause of primary open angle glaucoma in a large four-generation family with an apparent autosomal dominant mode of inheritance.
Twenty-three family members underwent comprehensive phenotyping by a single ophthalmologist, and the MYOC gene was sequenced in all affected family members for whom DNA was available. Parametric genomewide linkage analysis was performed on 10 affected family members and one unaffected family member. Within the critical region, mutation analysis of candidate genes LRP2BP, CYP4V2, and UFSP2 was carried out by direct sequencing.
No mutations were identified in MYOC. Genomewide linkage analysis generated one significant LOD score of 3.1 (maximum affected-only LOD score of 2.8) centered on chromosome 4 at 4q35.1-q35.2, a critical region that does not contain any of the previously reported primary open angle glaucoma loci. A 1.866-Mb (7.2 cM) region was identified containing 17 known or hypothetical genes. No mutations were identified in the candidate genes LRPB2BP, CYP4V2, and UFSP2.
This study identifies a new primary open angle glaucoma locus, GLC1Q, in a region on chromosome 4 not previously associated with glaucoma.
原发性开角型青光眼是最常见的青光眼类型，也是全球范围内导致不可逆性失明的主要原因。其遗传基础目前尚不清楚。在与这种疾病相关的 14 个位点中，仅鉴定出了两个基因，它们大约占病例的 4%。作者在一个具有明显常染色体显性遗传方式的四代大家庭中，研究了原发性开角型青光眼的遗传原因。
23 位家族成员由一位眼科医生进行了全面的表型分析，所有可获得 DNA 的受影响家族成员都对 MYOC 基因进行了测序。对 10 位受影响的家族成员和 1 位未受影响的家族成员进行了参数全基因组连锁分析。在关键区域内，通过直接测序对候选基因 LRP2BP、CYP4V2 和 UFSP2 进行了突变分析。
在 MYOC 中未发现突变。全基因组连锁分析产生了一个显著的 LOD 分数 3.1（最大受影响个体的 LOD 分数为 2.8），位于染色体 4 上的 4q35.1-q35.2 处，这是一个不包含任何先前报道的原发性开角型青光眼位点的关键区域。确定了一个包含 17 个已知或假设基因的 1.866-Mb（7.2cM）区域。在候选基因 LRPB2BP、CYP4V2 和 UFSP2 中未发现突变。
本研究在以前与青光眼无关的染色体 4 上的一个区域中，鉴定出了一个新的原发性开角型青光眼位点 GLC1Q。
