Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report
Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report
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KERA 基因的新变异导致中国家庭常染色体隐性角膜扁平症：病例报告
DOI：
10.3892/mmr.2019.10153
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发表时间：
2019-06-01
影响因子：
3.4
通讯作者：
Wu, Lingqian
中科院分区：
文献类型：
--
作者：
Huang, Chengzi;Long, Xigui;Wu, Lingqian
常染色体隐性遗传性扁平角膜是一种非常罕见的遗传性眼病，其特征是角膜曲率变平，由于屈光力低而导致明显的远视，并经常随之发生矫正性内斜视。其他特征包括各种角膜前段异常，无全身性问题。本研究的目的是探讨一个中国人扁平角膜家系的临床和分子改变。对患者进行全面的眼科检查，包括裂隙灯检查、眼底检查和眼部超声检查。全外显子组测序数据筛选先证者的病理变异，并通过桑格测序证实。一个新的错义突变，c.242A>G（p.N81S）和另一个新的7个碱基对缺失突变c.772- 779 del（p.G258Cfs*30），在角膜蛋白聚糖（KERA）基因中检测到;两个受影响的兄弟姐妹以复合杂合子状态遗传了这些变异，这些变异来自临床上未受影响的杂合子父亲（c.772_779del）和母亲（c.242A>G）。在不相关的健康对照（n=200）中未观察到突变。多个计算机软件预测支持这两种变体的致病性。此外，进行蛋白质建模预测以更好地理解角膜平坦的分子基础，特别是富含亮氨酸的重复结构域的重要性。据我们所知，这项研究是迄今为止在全球范围内发现的第14个致病性KERA突变，也是东亚地区的第一个。这些研究结果指导产前诊断的家庭问题和扩大的变异谱KERA，从而促进遗传咨询。
Autosomal recessive cornea plana is a very rare hereditary ocular disease, characterized by a flattened corneal curvature, marked hyperopia due to low refractive power and frequently consequent accommodative esotropia. Other features include various cornea anterior segment abnormalities, without systemic problems. The purpose of the present study was to investigate the clinical and molecular alterations in a Chinese family with cornea plana. Full ophthalmic examinations of the patients were performed, including slit-lamp examination, fundus examination and ocular ultrasound. Whole-exome sequencing data were screened for pathological variants in the proband, which were confirmed by Sanger sequencing. One novel missense mutation, c.242A>G (p.N81S) and another novel 7 base-pair deletion mutation, c.772-779del (p.G258Cfs*30), were detected in the keratocan (KERA) gene; two affected siblings inherited these variations in a compound heterozygous state, which were derived from the clinically unaffected heterozygous father (c.772_779del) and mother (c.242A>G), respectively. Neither mutation was observed in unrelated healthy controls (n=200). Multiple computer software predictions supported the pathogenicity of the two variants. Furthermore, protein modeling prediction was performed to better understand the molecular basis of cornea plana, particularly the importance of the leucine-rich repeat domain. This study presents the 14th pathogenic KERA mutations identified worldwide and the first in East Asia so far, to the best of our knowledge. These findings guided prenatal diagnosis for the family in question and expand on the variant spectrum of KERA, therefore facilitating genetic counseling.