Millá Elena, Mañé Begoña, Duch Susana, Hernan Imma, Borràs Emma, Planas Ester, Dias Miguel de Sousa, Carballo Miguel, Gamundi María José
Unidad de Glaucoma y Genética, Institut Comtal d'Oftalmologia, Barcelona, Spain.
Mol Vis. 2013 Aug 4;19:1707-22. Print 2013.
To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT).
Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others.
We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two).
The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1.
在患有不同临床类型家族性青光眼或高眼压症（OHT）的西班牙人群中鉴定肌纤蛋白（MYOC）和细胞色素P450 1B1（CYP1B1）突变。
来自226个家庭的索引患者参与了本研究。通过全面眼科检查诊断患者患有家族性青光眼或高眼压症。对207名索引患者进行了MYOC突变筛查：96例成人发病的原发性开角型青光眼（POAG）、21例原发性先天性青光眼（PCG）、18例青少年发病的开角型青光眼（JOAG）、5例Axenfeld-Rieger综合征（ARS）以及67例其他类型青光眼。其中102个家庭（包括所有检测到MYOC突变的家庭）也进行了CYP1B1突变筛查：45例POAG、25例PCG、21例JOAG、4例ARS以及7例其他类型。
我们检查了292名有青光眼或高眼压症家族史的个体（患者及其亲属）。我们在两个POAG家庭中鉴定出两个新的MYOC变异体，即p.Lys39Arg和p.Glu218Lys，以及在七个POAG（4个）、JOAG（1个）、PCG（1个）和正常眼压性青光眼（1个）家庭中鉴定出六个先前报道的MYOC突变。在16名索引患者中发现了CYP1B1突变，其中PCG（9例）、POAG（3例）、JOAG（2例）和ARS（2例）。
在非近亲先天性青光眼患者中发现的CYP1B1突变比例较高（9/25 = 36%），因此需要进行基因检测。然而，在我们的人群中，与青光眼相关的MYOC突变比例相对较低（9/207 = 4.4%）。即使在家族中，青光眼的可变表型表达也不能用MYOC和CYP1B1之间的双基因机制来解释。
