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Abstract：
Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution.
In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family.
This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.
In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family.
This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.
摘要：
角膜营养不良（CD）是一组异质的双侧，基因决定的，通常限于角膜的非炎性双侧角膜疾病。CD的特点是发病年龄的差异很大，进化和视觉冲击以及角膜不同深度不溶性沉积物的积累。临床症状显示双侧多发浅表，上皮，在该家族的三名患者中，不同严重程度的间质前颗粒混浊。共有99个基因参与CD。这项研究的目的是确定一个摩洛哥大家族中导致非典型角膜营养不良的致病变异，并描述具有严重不同进化阶段的临床表型。
在这项研究中,我们报告了一个带CD的摩洛哥大家庭。在三个受影响的成员中进行全外显子组测序（WES），这些成员在不同严重程度的阶段具有角膜营养不良的表型。通过Sanger测序对受影响的姐妹和母亲以及两个未受影响的兄弟进行了变体验证和家族隔离。全外显子组测序显示TGFBI基因中存在新的杂合突变(c.1772C>A;p.Ser591Tyr)。临床检查显示双侧多发浅表，在该家族的三名患者中，上皮和基质前颗粒混浊处于不同严重程度的阶段。
本报告描述了在受不同表型方面影响的三个家族成员中发现的TGFBI基因的新突变。这种突变与Thiel-Behnke角膜营养不良有关；因此，它可以被认为是一种新的表型基因型相关性，这将有助于这个家庭的遗传咨询。
在这项研究中,我们报告了一个带CD的摩洛哥大家庭。在三个受影响的成员中进行全外显子组测序（WES），这些成员在不同严重程度的阶段具有角膜营养不良的表型。通过Sanger测序对受影响的姐妹和母亲以及两个未受影响的兄弟进行了变体验证和家族隔离。全外显子组测序显示TGFBI基因中存在新的杂合突变(c.1772C>A;p.Ser591Tyr)。临床检查显示双侧多发浅表，在该家族的三名患者中，上皮和基质前颗粒混浊处于不同严重程度的阶段。
本报告描述了在受不同表型方面影响的三个家族成员中发现的TGFBI基因的新突变。这种突变与Thiel-Behnke角膜营养不良有关；因此，它可以被认为是一种新的表型基因型相关性，这将有助于这个家庭的遗传咨询。
