PDF(Pubmed)
Abstract：
Here, we have reported the genetic and clinical characteristics of four generations of a family patient from China with congenital fibrosis of extraocular muscles 1 (CFEOM1) and keratoconus (KC). The history of diseases, clinical observations, and blood samples of all family members were collected. A total of 100 healthy participants were recruited as normal controls. The whole exome sequencing of the genomic DNA and polymerase chain reaction were performed on samples obtained from the controls and their family members to verify the gene variants. The functional analyses of the variants were performed by using different software. Two single nucleotide polymorphisms were detected in the proband and other patients in his families, including a heterozygous missense variation, g.39726207C > T (c.2860C > T, p.R954W, rs121912585), in the third highly conserved coiled-coil domain of KIF21A, and a heterozygous missense variant, g.30664732A > C (c.136A > C, p.S46R, rs200111443) in TGFBR2. The variant p.R954W in KIF21A was predicted to be pathogenic using software, whereas p.S46R in TGFBR2 was predicted to be of uncertain significance (VUS). Thus, KC might have occurred in the proband and his daughter because of a combination of genetic mutations and involuntary eye rubbing induced by CFEOM1. This is the first case of concomitant KC in a family having CFEOM1. Thus, the study provides new information about patients with KC having CFEOM1. Furthermore, the study suggests that attention should be paid to the early detection and diagnosis of KC in patients with CFEOM1.
摘要：
这里,我们报道了来自中国的四代先天性眼外肌纤维化1（CFEOM1）和圆锥角膜（KC）患者的遗传和临床特征。疾病史,临床观察，收集所有家庭成员的血液样本。共招募100名健康参与者作为正常对照。对从对照及其家族成员获得的样品进行基因组DNA的全外显子组测序和聚合酶链反应以验证基因变体。通过使用不同软件进行变体的功能分析。在先证者及其家人中的其他患者中检测到两个单核苷酸多态性，包括杂合错义变异，g.39726207C>T(c.2860C>T,p.R954W,rs121912585),在KIF21A的第三个高度保守的卷曲螺旋结构域中，和杂合错义变体，g.30664732A>C(c.136A>C,p.S46R,rs200111443)在TGFBR2中。使用软件预测KIF21A中的变异体p.R954W具有致病性，而TGFBR2中的p.S46R预测具有不确定意义(VUS)。因此，KC可能发生在先证者和他的女儿中，原因是基因突变和CFEOM1诱导的非自愿眼部摩擦。这是在具有CFEOM1的家庭中伴随的KC的第一例。因此，该研究提供了KC患者CFEOM1的新信息.此外，该研究提示,应重视CFEOM1患者KC的早期发现和诊断.
