Skalicka Pavlina, Jedlickova Jana, Horinek Ales, Trkova Marie, Davidson Alice E, Tuft Stephen J, Dudakova Lubica, Liskova Petra
Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic.
Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic.
J Clin Med. 2022 Aug 31;11(17):5166. doi: 10.3390/jcm11175166.
We report the phenotype of a 15-year-old female patient with anterior segment dysgenesis (ASD) caused by a novel heterozygous loss-of-function variant. The proband underwent an ophthalmic examination as well as a molecular genetic investigation comprising exome sequencing, a single nucleotide polymorphism array to access copy number and Sanger sequencing to exclude non-coding causal variants. There was bilateral mild iris hypoplasia with pupil deformation and iridocorneal adhesions. In addition to these features of ASD, the corneas were flat, with mean keratometry readings of 38.8 diopters in the right eye and 39.5 diopters in the left eye. There was a snail track lesion of the left cornea at the level of the Descemet membrane. The central corneal endothelial cell density was reduced bilaterally at 1964 and 1373 cells/mm in the right and left eyes, respectively. Molecular genetic analysis revealed that the proband was a carrier of a novel heterozygous frameshifting variant in , c.605del p.(Pro202Argfs*113). Neither parent had this change, suggesting a de novo origin which was supported by paternity testing. We found no possibly pathogenic variants in the other genes associated with posterior corneal dystrophies or ASD. Further studies are warranted to verify whether there is a true association between snail track lesions, corneal flattening, and pathogenic variants in .
我们报告了一名15岁女性患者的表型，该患者因一种新的杂合功能丧失变异导致前段发育异常（ASD）。先证者接受了眼科检查以及分子遗传学研究，包括外显子组测序、用于检测拷贝数的单核苷酸多态性阵列和用于排除非编码致病变异的桑格测序。患者存在双侧轻度虹膜发育不全，伴有瞳孔变形和虹膜角膜粘连。除了这些ASD特征外，角膜扁平，右眼平均角膜曲率读数为38.8屈光度，左眼为39.5屈光度。左眼角膜后弹力层水平有蜗牛迹病变。双眼中央角膜内皮细胞密度均降低，右眼和左眼分别为1964个细胞/mm和1373个细胞/mm。分子遗传学分析显示，先证者是一种新的杂合移码变异c.605del p.(Pro202Argfs*113)的携带者。父母双方均无此变化，提示为新发突变，亲子鉴定支持这一结论。我们在与后部角膜营养不良或ASD相关的其他基因中未发现可能的致病变异。有必要进一步研究以验证蜗牛迹病变、角膜扁平与该基因中的致病变异之间是否存在真正的关联。
