scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yahya Benbouchta ◽  
Imane Cherkaoui Jaouad ◽  
Habiba Tazi ◽  
Hamza Elorch ◽  
Mouna Ouhenach ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background 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. Case presentation 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. Conclusions 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.

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy

2020 ◽  
Author(s):  
Yahya BENBOUCHTA ◽  
Imane CHERKAOUI JAOUAD ◽  
Habiba TAZI ◽  
Hamza ELORCH ◽  
Mouna OUHENACH ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background: Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, non-inflammatory bilateral corneal diseases which 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 of the cornea. Clinical symptoms revealed bilaterally multiple superficial, epithelial, and stromal anterior granular opacities, in different stages of severity among three patients of this family. 99 genes are involved in CDs.The aim of this study is to identify pathogenic variant caused atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with their severe different stages of evolution.Methods: 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 a corneal dystrophy in different stages of severity. De variant validation and familial segregation were done by Sanger sequencing in affected sister and mothers and in two unaffected brothers.Results: Whole exome sequencing showed a novel heterozygous mutation (c.1772C>A; p.Ser591Tyr) in TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities; in different stages of severity among three patients of this family. Conclusions: This report presents a novel mutation in TGFBI gene, found in three family members affected with different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy and therefore, it could be considered as a novel phenotype genotype correlation, which will help in genetic counseling for this family

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy

2020 ◽  
Author(s):  
Yahya BENBOUCHTA ◽  
Imane CHERKAOUI ◽  
Habiba TAZI ◽  
Hamza ELORCH ◽  
Mouna OUHENACH ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background: Corneal dystrophy (CDs) is a heterogeneous group disease, genetically determined non-inflammatory bilateral corneal diseases (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 of the cornea. Clinical symptoms revealed bilaterally multiple superficial, epithelial, and stromal anterior granular opacities, in different stages of severity among three patients of this family. 99 genes are involved in (CDs).The aim of this study is to identify pathogenic variant caused atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with their severe different stages of evolution.Methods: In this study, we report a large Moroccan family with fourteen individuals affected by corneal dystrophy. Whole Exome Sequencing (WES) was performed in the propositus (IV-7) which had corneal pain since the age of 18, associated with a decrease in visual acuity with anterior epithelial and stromal corneal dystrophy, in the form of microvacuole and poorly individualized anterior opacities, with fuzzy edges and an unevenness of the epithelial layers taking the sawtooth appearance. The familial segregation was done by Sanger sequencingResults: Whole exome sequencing showed a novel heterozygous mutation (c.1772C>A; p.Ser591Tyr) in TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities; in different stages of severity among three patients of this family. Conclusions: This report presents a novel mutation in TGFBI gene, found in all family members affects with different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy and therefore, it could be considered as a novel phenotype genotype correlation, which will help in genetic counseling for this family

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report

2020 ◽  
Author(s):  
Yahya BENBOUCHTA ◽  
Imane CHERKAOUI JAOUAD ◽  
Habiba TAZI ◽  
Hamza ELORCH ◽  
Mouna OUHENACH ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background: Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, non-inflammatory bilateral corneal diseases which 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 of the cornea. Clinical symptoms revealed bilaterally multiple superficial, epithelial, and stromal anterior granular opacities, in different stages of severity among three patients of this family. 99 genes are involved in CDs.The aim of this study is to identify pathogenic variant caused atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with their severe different stages of evolution.Case presentation: 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 a corneal dystrophy in different stages of severity. The variant validation and familial segregation were done by Sanger sequencing in affected sister and mothers and in two unaffected brothers. Whole exome sequencing showed a novel heterozygous mutation (c.1772C>A; p.Ser591Tyr) in TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities; in different stages of severity among three patients of this family. Conclusions: This report presents a novel mutation in TGFBI gene, found in three family members affected with different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy and therefore, it could be considered as a novel phenotype genotype correlation, which will help in genetic counseling for this family

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report.

2020 ◽  
Author(s):  
Yahya BENBOUCHTA ◽  
Imane CHERKAOUI JAOUAD ◽  
Habiba TAZI ◽  
Hamza ELORCH ◽  
Mouna OUHENACH ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background: Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, non-inflammatory bilateral corneal diseases which 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 of the cornea. Clinical symptoms revealed bilaterally multiple superficial, epithelial, and stromal anterior granular opacities, in different stages of severity among three patients of this family. 99 genes are involved in CDs.The aim of this study is to identify pathogenic variant caused atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with their severe different stages of evolution.Case presentation: 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 a corneal dystrophy in different stages of severity. The variant validation and familial segregation were done by Sanger sequencing in affected sister and mothers and in two unaffected brothers. Whole exome sequencing showed a novel heterozygous mutation (c.1772C>A; p.Ser591Tyr) in TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities; in different stages of severity among three patients of this family. Conclusions: This report presents a novel mutation in TGFBI gene, found in three family members affected with different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy and therefore, it could be considered as a novel phenotype genotype correlation, which will help in genetic counseling for this family

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report

2020 ◽  
Author(s):  
Yahya BENBOUCHTA ◽  
Imane CHERKAOUI JAOUAD ◽  
Habiba TAZI ◽  
Hamza ELORCH ◽  
Mouna OUHENACH ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Tgfbi Gene ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background: 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. Case presentation: 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. Conclusions: 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.

scholarly journals Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Qin Xiang ◽  
Lamei Yuan ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Yunfeiyang Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Transforming Growth Factor ◽  
Corneal Dystrophy ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Type I ◽  
Whole Exome ◽  
The Family

Background/Aims. Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods. A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results. Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C > T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions. The results suggested that the heterozygous TGFBI c.1663C > T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.

scholarly journals Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

2021 ◽  
Vol 22 (20) ◽  
pp. 11007
Author(s):  
Dżamila M. Bogusławska ◽  
Michał Skulski ◽  
Beata Machnicka ◽  
Stanisław Potoczek ◽  
Sebastian Kraszewski ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Mechanism ◽  
Whole Exome Sequencing ◽  
Genetic Basis ◽  
Hereditary Spherocytosis ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Functional Impairments ◽  
Whole Exome ◽  
Variable Clinical Presentation

Hereditary spherocytosis (HS), the most commonly inherited hemolytic anemia in northern Europeans, comprises a group of diseases whose heterogeneous genetic basis results in a variable clinical presentation. High-throughput genome sequencing methods have made a leading contribution to the recent progress in research on and diagnostics of inherited diseases and inspired us to apply whole exome sequencing (WES) to identify potential mutations in HS. The data presented here reveal a novel mutation probably responsible for HS in a single Polish family. Patients with clinical evidence of HS (clinical symptoms, hematological data, and EMA test) were enrolled in the study. The examination of the resulting WES data showed a number of polymorphisms in 71 genes associated with known erythrocyte pathologies (including membranopathies, enzymopathies, and hemoglobinopathies). Only a single SPTB gene variant indicated the possible molecular mechanism of the disease in the studied family. The new missense mutation p.C183Y was identified using WES in the SPTB gene, which is most likely the cause of clinical symptoms typical of hereditary spherocytosis (membranopathy) due to structural and functional impairments of human β-spectrin. This mutation allows for a better understanding of the molecular mechanism(s) of one of the membranopathies, hereditary spherocytosis.

scholarly journals A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

2021 ◽  
Author(s):  
Qing Li ◽  
Chengfeng Wang ◽  
Wei Li ◽  
Zaiqiang Zhang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Skin Biopsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Collagen Type Iv ◽  
Lacunar Infarcts ◽  
Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

Sign in / Sign up

Export Citation Format

Share Document