scholarly journals Whole exome sequencing identified a novel DAG1 mutation in a patient with rare, mild and late age of onset muscular dystrophy-dystroglycanopathy

2018 ◽  
Vol 23 (2) ◽  
pp. 811-818 ◽  
Author(s):  
Yi Dai ◽  
Shengran Liang ◽  
Xue Dong ◽  
Yanhuan Zhao ◽  
Haitao Ren ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Age Of Onset ◽  
Whole Exome

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.

A novel SYNE2 mutation identified by whole exome sequencing in a Korean family with Emery-Dreifuss muscular dystrophy

2020 ◽  
Vol 506 ◽  
pp. 50-54
Author(s):  
Sook Joung Lee ◽  
Sangjee Lee ◽  
Eunseok Choi ◽  
Soyoung Shin ◽  
Joonhong Park
Keyword(s):  
Muscular Dystrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Korean Family ◽  
Whole Exome

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 Homozygous missense variant in the TTN gene causing autosomal recessive limb-girdle muscular dystrophy type 10

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Amjad Khan ◽  
Rongrong Wang ◽  
Shirui Han ◽  
Muhammad Umair ◽  
Safdar Abbas ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Missense Variant ◽  
Pathogenic Variant ◽  
Limb Girdle Muscular Dystrophy ◽  
Molecular Diagnostic ◽  
Sequencing Analysis ◽  
Whole Exome

Abstract Background Limb-girdle muscular dystrophies (LGMDs) are large group of heterogeneous genetic diseases, having a hallmark feature of muscle weakness. Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10. The phenotypic spectrum of titinopathies is expanding, as next generation sequencing (NGS) technology makes screening of this large gene possible. Aim This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive LGMD type 10. Methods DNA from peripheral blood samples were obtained, whole exome sequencing (WES) was performed and several molecular and bioinformatics analysis were conducted to identify the pathogenic variant. TTN coding and near coding regions were further amplified using PCR and sequenced via Sanger sequencing. Results Whole exome sequencing analysis revealed a novel homozygous missense variant (c.98807G > A; p.Arg32936His) in the TTN gene in the index patients. No heterozygous individuals in the family presented LGMD features. The variant p.Arg32936His leads to a substitution of the arginine amino acid at position 32,936 into histidine possibly causing LGMD type 10. Conclusion We identified a homozygous missense variant in TTN, which likely explains LGMD type 10 in this family in line with similar previously reported data. Our study concludes that WES is a successful molecular diagnostic tool to identify pathogenic variants in large genes such as TTN in highly inbred population.

Whole-Exome Sequencing Identifies Small Mutations in Pakistani Muscular Dystrophy Patients

2021 ◽  
Vol 25 (3) ◽  
pp. 218-226
Author(s):  
Mehwish Zehravi ◽  
Mohsin Wahid ◽  
Junaid Ashraf ◽  
Tehseen Fatima
Keyword(s):  
Muscular Dystrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome

scholarly journals Whole Exome Sequencing Aids The Diagnosis of Fetal Skeletal Dysplasia

2020 ◽  
Author(s):  
Hui Tang ◽  
Qin Zhang ◽  
Linliang Yin ◽  
Jingjing Xiang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Skeletal Dysplasia ◽  
Clinical Symptoms ◽  
Single Nucleotide Polymorphism Array ◽  
Snp Array ◽  
Somatic Mosaicism ◽  
Single Nucleotide ◽  
Whole Exome

Abstract Background: Skeletal dysplasia is a complex group of bone and cartilage disorders with strong clinical and genetical heterogeneousity. Several types have prenatal phenotypes. And it is difficult to make a molecular diagnosis rapidly due to lacking family history and non-specific and limited clinical symptoms in utero. This study aims to diagnose 16 Chinese fetuses with skeletal dysplasia.Methods: Single nucleotide polymorphism-array (SNP-array) was performed in 12 of 16 samples. If no microdeletions or microreplications related to skeletal dysplasia were detected, whole-exome sequencing (WES) was adopted. And the last four cases only got whole-exome sequencing for analyzing copy number variants and single nucleotide variations at the same time.Results: Among the 16 cases, 12 patients received definitive diagnosis and we detected one deletion in DMD gene by SNP-array and 15 variants of 6 genes including FGFR3, COL1A1, COL1A2, ALPL, HSPG2 and DYNC2H1. 8 variants of COL1A1, COL1A2, ALPL and HSPG2 are novel. And somatic mosaicism in asymptomatic parent with mutations in COL1A1 or COL1A2 was observed.Conclusions: In general, our study expanded the prenatal phenotypes in Duchenne muscular dystrophy (DMD)/ Becker muscular dystrophy (BMD), found 8 novel variants and elucidated that the utilization of whole-exome sequencing improved the diagnosis yield of skeletal dysplasia and provided useful genetic counseling guidance for parents.

scholarly journals Case Report: Whole-Exome Sequencing With MLPA Revealed Variants in Two Genes in a Patient With Combined Manifestations of Spinal Muscular Atrophy and Duchenne Muscular Dystrophy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Xia ◽  
Yijie Feng ◽  
Lu Xu ◽  
Xiaoyang Chen ◽  
Feng Gao ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Spinal Muscular Atrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Muscular Atrophy ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Chinese Family ◽  
Whole Exome

Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are two common kinds of neuromuscular disorders sharing various similarities in clinical manifestations. SMA is an autosomal recessive genetic disorder that results from biallelic mutations of the survival motor neuron 1 gene (SMN1; OMIM 600354) on the 5q13 chromosome. DMD is an X-linked disorder caused by defects in the DMD gene (OMIM 300377) on the X chromosome. Here, for the first time, we report a case from a Chinese family who present with clinical manifestations of both two diseases, including poor motor development and progressive muscle weakness. We identified a homozygous deletion in exons 7 and 8 of the SMN1 gene and a deletion in exon 50 of the DMD gene by whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA). This case expands our understanding of diagnosis for synchronous SMA and DMD and highlights the importance of various genetic testing methods, including WES, in differential diagnosis of neuromuscular diseases.

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