Chaudhuri Zia, John Jibin, Aneja Satinder, Thelma B K
a Lady Hardinge Medical College , University of Delhi , New Delhi , India.
b Department of Genetics , University of Delhi South Campus , New Delhi, India.
Strabismus. 2017 Dec;25(4):200-213. doi: 10.1080/09273972.2017.1350865. Epub 2017 Aug 10.
Familial clustering of common forms of primary strabismus like esotropia (ET) and exotropia (XT) is observed in a proportion of the strabismus cohort. The genetic components of this remain unidentified. Linkage studies have demonstrated susceptibility locus for primary strabismus at the STBMS1 locus on 7p22.1 as well as other loci on 4q28.3 and 7q31.2. Recently next generation sequencing (NGS) technology has emerged as a powerful tool in discovery genomics and a large number of novel disease-causing variants are being reported. In this study, we recruited informative families for subsequent genetic analysis for disease-causing variant identification.
All consecutive families with two or more affected members with primary concomitant horizontal strabismus were prospectively recruited at the ophthalmic outpatients department (OPD) of Lady Hardinge Medical College, New Delhi, from August 2014 to February 2017. Detailed phenotypic evaluation and pedigree documentation was performed.
Of the 39 recruited families of north Indian origin, 18 families each had affected family members demonstrating either ET or XT. 100% concordance of the phenotype in the affected family members was observed in these families. While vertical transmission was observed in 17/18 families with XT, 7 with ET had affected members across one generation, 2 demonstrated consanguineous pedigree, and 2 comprised identical twin families. In 3 families, a combination of ET and XT was noted. This comprised one family with the ET and XT patients being from 2 separate arms of the family related by marriage, one family where one sibling had XT and the other had ET, and another family where the maternal aunt of the affected proband with ET had XT.
Subjects with familial primary concomitant strabismus recruited in this study may provide a valuable resource to unravel the genetic determinants of this condition, which is a common disorder of early childhood with high ophthalmic morbidity.
在斜视患者队列中，观察到一部分内斜视（ET）和外斜视（XT）等常见原发性斜视形式存在家族聚集现象。其遗传成分尚未明确。连锁研究已证明原发性斜视的易感基因座位于7p22.1的STBMS1基因座以及4q28.3和7q31.2的其他基因座。最近，下一代测序（NGS）技术已成为发现基因组学中的强大工具，大量新的致病变异不断被报道。在本研究中，我们招募了信息丰富的家系进行后续遗传分析，以鉴定致病变异。
2014年8月至2017年2月，在新德里哈丁夫人医学院眼科门诊前瞻性招募所有有两名或更多原发性共同性水平斜视受累成员的连续家系。进行了详细的表型评估和系谱记录。
在招募的39个北印度血统家庭中，18个家庭有受累家庭成员表现为ET或XT。在这些家庭中，受累家庭成员的表型一致性达100%。在17/18个XT家庭中观察到垂直遗传，7个ET家庭中有受累成员跨越一代，2个显示近亲系谱，2个由同卵双胞胎家庭组成。在3个家庭中，注意到ET和XT的组合。其中一个家庭中，ET和XT患者来自通过婚姻相关的家族的两个不同分支；一个家庭中，一个兄弟姐妹有XT，另一个有ET；另一个家庭中，患有ET的先证者的姨妈有XT。
本研究中招募的家族性原发性共同性斜视患者可能为揭示这种疾病的遗传决定因素提供宝贵资源，这种疾病是幼儿期常见疾病，眼科发病率高。
