Department Of Anatomy, Laboratory for Molecular Reproduction and Genetics, AIIMS, Ansari Nagar, New Delhi 110029, India.
J Glaucoma. 2010 Aug;19(6):398-404. doi: 10.1097/IJG.0b013e3181c4ae74.
Sturge-Weber syndrome (SWS) is a progressive condition of mesodermal phakomatosis. This preliminary study is the first report of CYP1B1 mutation analysis in SWS with congenital glaucoma.
Mutations in CYP1B1 gene are the major cause of congenital glaucoma. CYP1B1 is involved in metabolism of melatonin, retinol, and other endogenous/exogenous substrates. Mutations in CYP1B1 adversely affect signal transduction pathways and thus impair development/differentiation of anterior segment structures. This results in impaired aqueous outflow. CYP1B1 has higher expression in fetal eyes and plays major role in morphogenesis of iris, ciliary body, and anterior chamber angle. Hence, we decided to evaluate SWS cases with buphthalmos for 6 most prevalent CYP1B1 mutations by polymerase chain reaction-restriction-fragment length polymorphism followed by sequencing. Trabecular meshwork was studied for morphological alterations by scanning electron microscopy.
All patients had normal 46, XY karyotype. Polymerase chain reaction-restriction-fragment length polymorphism showed CYP1B1 mutations in 2 of 5 SWS cases. Scanning electron microscopy findings were suggestive of trabecular dysgenesis.
No CYP1B1 mutation has been reported in any SWS case till date because syndromic cases were not analyzed for mutations in earlier studies. Earlier studies have reported that onset of glaucoma in SWS shows a bimodal pattern. The results from this pilot study show that SWS cases with gyral calcification, buphthalmos, and early onset glaucoma should be analyzed for CYP1B1 mutations. The effect of vascular malformation-induced venous engorgement and raised intraocular pressure may only be additive and may result in a much more severe phenotype.
SWS with buphthalmos and gyral calcification should undergo CYP1B1 mutation analysis to identify an underlying genetic pathology for glaucoma. This will aid in determining the prognosis and management and will also help to provide comprehensive counseling in such cases.
CYP1B1 基因突变是先天性青光眼的主要原因。CYP1B1 参与褪黑素、视黄醇和其他内源性/外源性底物的代谢。CYP1B1 基因突变会对信号转导途径产生不利影响，从而损害前节结构的发育/分化。这导致房水流出受阻。CYP1B1 在胎儿眼中表达较高，在虹膜、睫状体和前房角的形态发生中起主要作用。因此，我们决定通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）后测序，评估 5 例伴有牛眼的 Sturge-Weber 综合征（SWS）病例中 6 种最常见的 CYP1B1 突变。通过扫描电子显微镜研究小梁网的形态改变。
所有患者均具有正常的 46，XY 核型。PCR-RFLP 显示 5 例 SWS 病例中有 2 例存在 CYP1B1 突变。扫描电子显微镜检查结果提示小梁发育不良。
迄今为止，尚无任何 SWS 病例报告 CYP1B1 突变，因为早期研究中未对综合征病例进行突变分析。早期研究报告称，SWS 患者的青光眼发病呈双峰模式。本研究结果表明，具有脑回钙化、牛眼和早发性青光眼的 SWS 病例应分析 CYP1B1 突变。血管畸形引起的静脉充血和眼压升高的影响可能只是相加的，可能导致更严重的表型。
伴有牛眼和脑回钙化的 SWS 应进行 CYP1B1 突变分析，以确定潜在的遗传病理学青光眼。这将有助于确定预后和管理，并有助于在这些情况下提供全面咨询。
