Zhang Lu-Si, Li Hai-Bo, Zeng Jun, Yang Yan, Ding Chun
Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.
Hunan Clinical Research Center of Ophthalmic Disease, Changsha 410011, Hunan Province, China.
Int J Ophthalmol. 2018 Jun 18;11(6):918-922. doi: 10.18240/ijo.2018.06.04. eCollection 2018.
To explore the clinical feature and genetic etiology of a Chinese Knobloch syndrome family.
Ocular examinations and magnetic resonance imagings (MRIs) were performed on the family. Whole exome sequencing was conducted on the two patients. Sanger sequencing was utilized to validate the presence of variation in the family as well as in 100 normal controls. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression level of in peripheral blood lymphocytes of the patients and normal carriers.
The affected subjects presented with vision loss, exotropia, cataracts, retinal detachment, and other complications. A homozygous c.4759_4760delCT (p.Leu1587ValfsX72) mutation (rs398122391) in was identified in the two patients, cosegregating with the phenotypes, and did not be detected in 100 normal controls. This mutation caused significant decreased expression of mRNA in the patients.
The findings strongly indicate that this mutation is the disease-causing mutation. Moreover, this is the first Knobloch syndrome pedigree reported in the Chinese population.
探究一个中国诺布洛赫综合征家系的临床特征及遗传病因。
对该家系进行眼科检查及磁共振成像（MRI）检查。对两名患者进行全外显子组测序。采用桑格测序法验证该家系及100名正常对照中变异的存在情况。运用实时定量聚合酶链反应（PCR）检测患者及正常携带者外周血淋巴细胞中[具体基因名称未给出]的表达水平。
患病个体出现视力丧失、外斜视、白内障、视网膜脱离及其他并发症。在两名患者中鉴定出[具体基因名称未给出]的纯合c.4759_4760delCT（p.Leu1587ValfsX72）突变（rs398122391），该突变与表型共分离，且在100名正常对照中未检测到。此突变导致患者中[具体基因名称未给出]mRNA的表达显著降低。
这些发现有力地表明该突变是致病突变。此外，这是中国人群中报道的首个诺布洛赫综合征家系。
