scholarly journals Compound pathogenic mutation in the USH2A gene in Chinese RP families detected by whole‑exome sequencing

2018 ◽  
Author(s):  
Yue‑Chuan Fu ◽  
Na Chen ◽  
Zi‑Long Qiu ◽  
Lin Liu ◽  
Jie Shen
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pathogenic Mutation ◽  
Whole Exome

scholarly journals Clinical and Molecular Characterization of Qatari Patients with Inherited Dysfibrinogenemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1037-1037
Author(s):  
Amna Gameil ◽  
Hajer Al-Mulla ◽  
Aliaa Amer ◽  
Tawfeg Ben-Omran ◽  
Mohamed A Yassin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Pathogenic Mutation ◽  
Functional Assay ◽  
Sequencing Analysis ◽  
Thrombin Time ◽  
Whole Exome ◽  
Antigen Assay

Abstract Background and Objectives: Inherited Dysfibrinogenemia is a rare functional fibrinogen disorder in which the fibrinogen protein is present but with a reduced function. Fibrinogen is a 340-kDa glycoprotein that is encoded by three genes namely: Fibrinogen Bb (FGB), Aa (FGA), and g (FGG). The disorder is characterized by a wide spectrum of clinical phenotypes, ranging from asymptomatic to mild- to-severe bleeding or thrombotic manifestations and recurrent miscarriages. The mode of inheritance is mostly autosomal dominant manner and frequently as a result of a point mutation in FGA (Arg35) and FGG (Arg301). The laboratory diagnosis is based on discrepancy between fibrinogen antigen (detected by immunoassay or by immuno-turbidimetric assay) and functional assay (detected by Clauss method or other clot-based assays). The disorder is often associated with prolonged activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT).Fibrinogen activity is reduced by Clauss method while the antigen assay remains normal. The management is directed towards prevention of bleeding with prophylactic fibrinogen concentrates or cryoprecipitate prior to invasive procedures, surgeries or delivery. Dysfibrinogenemia is a rare disorder yet it is very prevalent in Qatar as a result of high rate of consanguineous marriages. The aim of our study is to describe the clinical phenotype in relation to genotype in this cohort. Methods We conducted a retrospective analysis of 23 patients with Inherited Dysfibrinogenemia reported by our center from 2015 to 2020 . Patients with a positive family of history fibrinogen disorder and abnormal coagulation screen, low functional fibrinogen assay (by Clauss method) or normal antigen level by turbidimetry were included. Whole exome sequencing (WES) was performed on the proband case which detected a likely pathogenic mutation that was tested on subsequent cases. We diagnosed our patients with Inherited Dysfibrinogenemia based on both coagulation-based assays and molecular tests. Probable Inherited Dysfibrinogenemia was considered in patients where the molecular test or antigen assay were not performed. To assess the clinical phenotype, data was collected that included; age at diagnosis, gender, bleeding and thrombotic events as well as coagulation screening. (Table 1) Results 23 patients who were described in this cohort belong to the same tribe. 74% (17 o/23) were female and only 41% (7/17) reported an obstetric bleeding (postpartum or post abortion) and one reported mild bleeding that occurred in the postmenopausal period and no previous bleeding (case#19). The median age of diagnosis was 28.8 years (5-69) for the females. All male cases in the cohort were detected either during routine screening or prior to surgery with no previous history of bleeding. No thrombotic events were observed in this cohort. Genetic Analysis Following proper genetic counseling and informed consent, whole exome sequencing analysis (WES) was performed on the index case which included testing of the fibrinogen genes FGA, FGB and FGG. WES revealed a likely pathogenic mutation in the FGA gene (p. Arg35His (R35H) (CGT>CAT): c.104 G>A in exon 2)-Located within the cleavage site of fibrinopeptide A by thrombin (The UniProt Consortium, 2017), which is a mutational hotspot. This result is likely consistent with the diagnosis of Dysfibrinogenemia. Conclusion The FGA R35H mutation is considered a probable recurrent variant in a large tribe in the Qatari population and is associated with late onset mild bleeding manifestations in minority of cases . Despite the fact that the reported tribe is highly consanguineous, the R35H mutation behaved in an autosomal dominant manner rather than recessive in this cohort.Further studies to assess phenotype - genotype correlation of Dysfibrinogenemia is warranted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of a de novo mutation in KRT5 gene underlying epidermolysis bullosa simplex by whole exome sequencing in a Vietnamese patient

2021 ◽  
Vol 19 (2) ◽  
pp. 223-228
Author(s):  
Ma Thi Huyen Thuong ◽  
Dang Tien Truong ◽  
Nguyen Hai Ha ◽  
Nguyen Dang Ton
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epidermolysis Bullosa ◽  
De Novo ◽  
Recurrence Risk ◽  
Pathogenic Mutation ◽  
De Novo Mutation ◽  
Causative Mutation ◽  
Epidermolysis Bullosa Simplex ◽  
Whole Exome

Epidermolysis bullosa simplex (EBS) is a group of epidermolysis bullosa (EB) and accounts for 75-85% EB cases. Most EBS patients are caused by mutations in KRT5 or KRT14, encoding for keratin 5 and keratin 14, respectively, which impair the structural entirety of paired intermediate filaments expressed in the fracture of basal keratinocytes and subsequent blistering of the epithelium. This study aimed to identify the causative mutation in a Vietnamese EB case. Whole exome sequencing (WES) was performed in the affected individual and revealed a de novo heterozygous pathogenic mutation in exon 7 of KRT5 gene, resulting in an amino acid change at position 477, with glutamic acid to lysine substitution (p.E477K). The KRT5 p.E477K was strong associated with the very severe or lethal of generalized severe EBS (GS-EBS), characterized by the severe symptoms at birth, improving with age and evolution to palmoplantar keratoderma and nail dysplasia. Our finding will aid the molecular diagnosis, prognosis prediction of the patient with GS-EBS due to p.E477K and significant genetic counselling the family concerning the recurrence risk for future pregnancies.

scholarly journals Clinical Whole-Exome Sequencing Analysis Reveals a Novel Missense COL11A1 Mutation Resulting in an 18-Week Iranian Male Aborted Fetus with Fibrochondrogenesis 1: A Case Report

2021 ◽  
Author(s):  
Hanifeh Mirtavoos-Mahyari ◽  
Sanaz Ajami ◽  
Amirhosein Mehrtash ◽  
Seyedeh Mahya Marashiyan ◽  
Farbod Bahreini ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Missense Variant ◽  
Pathogenic Mutation ◽  
Sequencing Analysis ◽  
Gene Encoding ◽  
Protein Levels ◽  
Proper Role ◽  
Whole Exome

Abstract BackgroundFibrochondrogenesis 1, an autosomal recessive syndrome, is an infrequent and rare disease, causing short-limbed skeletal dysplasia. This syndrome is clinically characterized and distinguished by a small nose and anteverted bares, flat midface, shortened long bones, and a protuberant abdomen. Mutations in the gene encoding the α1 chain of type XI collagen (COL11A1) are seen to be the main cause of this disease.Case PresentationWe present an 18-week Iranian male aborted fetus with Fibrochondrogenesis 1 from consanguineous parents. Whole-exome sequencing (WES) revealed a novel missense variant from G to A in exon 45 of 68 in the COL11A1 gene (NM_080629.2: c.3440G>A, [p.G1147E, g.103404625]). The mutation was confirmed by Sanger sequencing and further, MutationTaster predicted this variant to be disease-causing.ConclusionBioinformatic analysis suggests that this variant is highly conserved in both nucleotide and protein levels, suggesting that it has an important function in the proper role of COL11A1 protein. In-silico analysis suggests that this mutation alters the COL11A1 protein structure through a Glycine to Glutamic acid substitution. This is a novel mutation and a rare variant as this variant is not reported in gmomAD, ExAC, or 1000 genome databases.To the best of the authors’ knowledge, this is the first study to report a novel pathogenic mutation in COL11A1 in association with Fibrochondrogenesis 1. Therefore, we suggest that WES can be used as a robust method to achieve rapid diagnosis and identification of pathogenic and novel mutations in patients.

Whole-Exome Sequencing Identifies a Novel Mutation (p.L320R) of Alpha-Actinin 2 in a Chinese Family with Dilated Cardiomyopathy and Ventricular Tachycardia

2019 ◽  
Vol 157 (3) ◽  
pp. 148-152 ◽  
Author(s):  
Liang-Liang Fan ◽  
Hao Huang ◽  
Jie-Yuan Jin ◽  
Jing-Jing Li ◽  
Ya-Qin Chen ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Dilated Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Pathogenic Mutation ◽  
Left Ventricular ◽  
Chinese Family ◽  
Whole Exome

Dilated cardiomyopathy (DCM) is a severe cardiovascular disease which can lead to heart failure and sudden cardiac death (SCD). The typical feature of DCM is left ventricular enlargement or dilatation. In some conditions, DCM and arrhythmia can occur concurrently, apparently promoting the prevalence of SCD. According to previous studies, mutations in more than 100 genes have been detected in DCM and/or arrhythmia patients. Here, we report a Chinese family with typical DCM, ventricular tachycardia, syncope, and SCD. Using whole-exome sequencing, a novel, likely pathogenic mutation (c.959T>G/p.L320R) of actinin alpha 2 (ACTN2) was identified in all affected family members. This novel mutation was also predicted to be disease-causing by MutationTaster, SIFT, and Polyphen-2. Our study not only expands the spectrum of ACTN2 mutations and contributes to the genetic diagnosis and counseling of the family, but also provides a new case with overlap phenotype that may be caused by the ACTN2 variant.

Whole exome sequencing identified a pathogenic mutation in RYR2 in a Chinese family with unexplained sudden death

2018 ◽  
Vol 51 (2) ◽  
pp. 309-315 ◽  
Author(s):  
Yubi Lin ◽  
Siqi He ◽  
Zili Liao ◽  
Ruiling Feng ◽  
Ruilin Liu ◽  
...  
Keyword(s):  
Sudden Death ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pathogenic Mutation ◽  
Chinese Family ◽  
Whole Exome
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