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 Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guangxian Yang ◽  
Yi Yin ◽  
Zhiping Tan ◽  
Jian Liu ◽  
Xicheng Deng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Renal Malformations

Abstract Background Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. Methods A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. Results Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. Conclusions This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

scholarly journals Whole-exome Sequencing Identified a Novel Heterozygous Mutation of SALL1 and a New Homozygous Mutation of PTPRQ in a Chinese Family With Townes-brocks Syndrome and Hearing Loss

2021 ◽  
Author(s):  
Yang Guangxian ◽  
Yin Yi ◽  
Tan Zhiping ◽  
Liu Jian ◽  
Deng Xicheng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Renal Malformations

Abstract Background: Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease (CHD). In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns.Methods: A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss.Results: Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation (ENST00000266688: c.1057_1057delC, p. L353SfsX8)) of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis.Conclusions: This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

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.

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 A Novel BBS9 Mutation Identified via Whole-Exome Sequencing in a Chinese Family with Bardet-Biedl Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Yue Zhang ◽  
Manhong Xu ◽  
Minglian Zhang ◽  
Guoxing Yang ◽  
Xiaorong Li
Keyword(s):  
Mental Retardation ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Cone Dystrophy ◽  
Bardet Biedl Syndrome ◽  
Homozygous Variant ◽  
Whole Exome

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by polydactyly, obesity, rod-cone dystrophy, and mental retardation. Twenty-one genes have been identified as causing BBS. This study collected a BBS pedigree from two patients and performed whole-exome sequencing on one patient. We identified a novel homozygous variant c.1114C>T (p.Q372X) in the BBS9 of the two siblings. This variant was confirmed and completely cosegregated with the disease of this family by Sanger sequencing. We report a novel homozygous variant c.1114C>T in the BBS9 gene in a Chinese 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 A Novel Missense Variant of TP63 Heterozygously Present in Split-Hand/Foot Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Hao Geng ◽  
Dongdong Tang ◽  
Chuan Xu ◽  
Xiaojin He ◽  
Zhiguo Zhang
Keyword(s):  
Blood Sample ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Peripheral Blood ◽  
Sanger Sequencing ◽  
Missense Variant ◽  
Chinese Family ◽  
Peripheral Blood Sample ◽  
Whole Exome ◽  
Novel Variant

Background. Split-hand/foot malformation (SHFM) is a severe congenital disability mainly characterized by the absence or hypoplasia of the central ray of the hand/foot. To date, several candidate genes associated with SHFM have been identified, including TP63, DLX5, DLX6, FGFR1, and WNT10B. Herein, we report a novel variant of TP63 heterozygously present in affected members of a family with SHFM. Methods. This study investigated a Chinese family, in which the proband and his son suffered from SHFM. The peripheral blood sample of the proband was used to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease. Postsequencing bioinformatic analyses and Sanger sequencing were conducted to verify the identified variants and parental origins on all family members in the pedigree. Results. By postsequencing bioinformatic analyses and Sanger sequencing, we identified a novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in this family that results in a substitution of methionine with isoleucine, which is probably associated with the occurrence of SHFM. Conclusion. A novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in SHFM was thus identified, which may enlarge the spectrum of known TP63 variants and also provide new approaches for genetic counselling of families with SHFM.

scholarly journals A Novel CRYBB2 Stopgain Mutation Causing Congenital Autosomal Dominant Cataract in a Chinese Family

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Zhou ◽  
Yaru Zhai ◽  
Lulin Huang ◽  
Bo Gong ◽  
Jie Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Family Members ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Whole Exome ◽  
Causal Mutation ◽  
Control Samples

Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T<G (p.E167X) in CRYBB2 gene was found. And the results showed that the mutation cosegregated with the disease phenotype in the family and was absolutely absent in 1000 ethnicity-matched control samples. Thus, the heterozygous mutation c.499T<G (p.E167X) in CRYBB2 was the causal mutation responsible for this ADCC family. In conclusion, our findings revealed a novel stopgain mutation c.499T<G (p.E167X) in the exon 6 of CRYBB2 which expanded the mutation spectrum of CRYBB2 in Chinese congenital cataract population and illustrated the important role of CRYBB2 in the genetics research of congenital cataract.

scholarly journals Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Qin Xiang ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Yi Guo ◽  
Zhijian Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Retinal Pigment ◽  
Han Chinese ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Stargardt Disease ◽  
Pathogenic Variants ◽  
Whole Exome

Abstract Stargardt disease (STGD1, OMIM 248200) is a common hereditary juvenile or early adult onset macular degeneration. It ultimately leads to progressive central vision loss. Here, we sought to identify gene mutations associated with STGD1 in a three-generation Han Chinese pedigree by whole exome sequencing and Sanger sequencing. Two novel potentially pathogenic variants in a compound heterozygous state, c.3607G>T (p.(Gly1203Trp)) and c.6722T>C (p.(Leu2241Pro)), in the ATP binding cassette subfamily A member 4 gene (ABCA4) were identified as contributing to the family’s STGD1 phenotype. These variants may impact the ABCA4 protein structure and reduce the retinal-activated ATPase activity, leading to abnormal all-trans retinal accumulation in photoreceptor outer segments and in retinal pigment epithelium cells. The present study broadens the mutational spectrum of the ABCA4 responsible for STGD1. A combination of whole exome sequencing and Sanger sequencing is likely to be a time-saving and cost-efficient approach to screen pathogenic variants in genetic disorders caused by sizable genes, as well as avoiding misdiagnosis. These results perhaps refine genetic counseling and ABCA4-targetted treatments for families affected by STGD1.

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