Ergun Sezen Guntekin, Akay Guvem Gumus, Ergun Mehmet Ali, Perçin E Ferda
Department of Biological Sciences, Middle East Technical University (METU), Ankara, Turkey; Gazi University Faculty of Medicine, Department of Medical Genetics, Besevler, Ankara, Turkey.
Brain Research Centre, Ankara University, Mamak, Ankara, Turkey.
Eur J Med Genet. 2017 Mar;60(3):200-204. doi: 10.1016/j.ejmg.2017.01.007. Epub 2017 Jan 19.
Microphthalmia is defined as the measurement of the total axial length of the eyeball to be below average of the two standard deviation according to the age. While several genes have been identified so far related to microphthalmia, the genetic etiology of the disease has not been fully understood because of genetic heterogeneity observed in this disease. After exclusion of the genes that had been known to be the cause of microphthalmia, we performed homozygosity mapping and exome sequencing to clarify the genetic etiology of the bilateral microphthalmia in this family. When the results of the exome and microarray data were considered together as a splice-site mutation in LRP5 gene [c.2827 + 1G > A], which is known to be important for eye development and Wnt receptor signaling pathway, was found to be the cause of microphthalmia in our family. It was understood that after finding this mutation, when bone mineral density was measured with DXA in the family whose ages range between 19 and 28 and who have no bone problem before, osteoporosis was diagnosed. It was also understood that microphthalmia found in this family is a clinical finding of OPPG syndrome.
小眼症的定义是根据年龄，眼球总眼轴长度的测量值低于平均水平两个标准差。虽然目前已经鉴定出几个与小眼症相关的基因，但由于该疾病存在遗传异质性，其遗传病因尚未完全明确。在排除已知导致小眼症的基因后，我们进行了纯合子定位和外显子组测序，以明确该家族双侧小眼症的遗传病因。当将外显子组和微阵列数据的结果综合考虑时，发现LRP5基因中的一个剪接位点突变[c.2827 + 1G > A]是我们家族中小眼症的病因，已知该基因对眼睛发育和Wnt受体信号通路很重要。据了解，发现该突变后，在年龄介于19至28岁且此前无骨骼问题的家族成员中，通过双能X线吸收法（DXA）测量骨密度时，诊断出了骨质疏松症。还了解到该家族中发现的小眼症是骨质疏松 - 假性神经胶质瘤综合征（OPPG综合征）的一个临床症状。
