Whole exome sequencing identified FAM149A as a plausible causative gene for congenital hereditary endothelial dystrophy, affecting Nrf2-Antioxidant signaling upon oxidative stress

2021 ◽  
Author(s):  
Jing Zhang ◽  
Yiqin Dai ◽  
Dan Wu ◽  
Yue Li ◽  
Jianjiang Xu
Keyword(s):  
Oxidative Stress ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Causative Gene ◽  
Whole Exome ◽  
Congenital Hereditary Endothelial Dystrophy

DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing

2018 ◽  
Vol 55 (3) ◽  
pp. 198-204 ◽  
Author(s):  
Wen-Bin He ◽  
Chao-Feng Tu ◽  
Qiang Liu ◽  
Lan-Lan Meng ◽  
Shi-Min Yuan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Male Patient ◽  
Histological Analysis ◽  
Pedigree Analysis ◽  
Obstructive Azoospermia ◽  
Ovarian Insufficiency ◽  
Causative Gene ◽  
Whole Exome

BackgroundThe genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown.ObjectiveTo identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family.MethodsWe performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA.ResultsWe identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I.ConclusionsTo the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.

Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients

2016 ◽  
Vol 31 (14) ◽  
pp. 1534-1539 ◽  
Author(s):  
Maya Kuperberg ◽  
Dorit Lev ◽  
Lubov Blumkin ◽  
Ayelet Zerem ◽  
Mira Ginsberg ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Genetic Diagnosis ◽  
Clinical Feature ◽  
Causative Gene ◽  
High Detection Rate ◽  
Whole Exome ◽  
Neurological Patients ◽  
Low Costs

Whole exome sequencing enables scanning a large number of genes for relatively low costs. The authors investigate its use for previously undiagnosed pediatric neurological patients. This retrospective cohort study performed whole exome sequencing on 57 patients of “Magen” neurogenetic clinics, with unknown diagnoses despite previous workup. The authors report on clinical features, causative genes, and treatment modifications and provide an analysis of whole exome sequencing utility per primary clinical feature. A causative gene was identified in 49.1% of patients, of which 17 had an autosomal dominant mutation, 9 autosomal recessive, and 2 X-linked. The highest rate of positive diagnosis was found for patients with developmental delay, ataxia, or suspected neuromuscular disease. Whole exome sequencing warranted a definitive change of treatment for 5 patients. Genetic databases were updated accordingly. In conclusion, whole exome sequencing is useful in obtaining a high detection rate for previously undiagnosed disorders. Use of this technique could affect diagnosis, treatment, and prognostics for both patients and relatives.

scholarly journals Identification of two novel pathogenic variants of PIBF1 by whole exome sequencing in a 2-year-old boy with Joubert syndrome

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yue Shen ◽  
Hao Wang ◽  
Zhimin Liu ◽  
Minna Luo ◽  
Siyu Ma ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Autosomal Recessive Inheritance ◽  
Joubert Syndrome ◽  
Causative Gene ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Syndrome Individual

Abstract Background Joubert syndrome (OMIM 213300) is an autosomal recessive disorder with gene heterogeneity. Causal genes and their variants have been identified by sequencing or other technologies for Joubert syndrome subtypes. Case presentation A two-year-old boy was diagnosed with Joubert syndrome by global development delay and molar tooth sign of mid-brain. Whole exome sequencing was performed to detect the causative gene variants in this individual, and the candidate pathogenic variants were verified by Sanger sequencing. We identified two pathogenic variants (NM_006346.2: c.1147delC and c.1054A > G) of PIBF1 in this Joubert syndrome individual, which is consistent with the mode of autosomal recessive inheritance. Conclusion In this study, we identified two novel pathogenic variants in PIBF1 in a Joubert syndrome individual using whole exome sequencing, thereby expanding the PIBF1 pathogenic variant spectrum of Joubert syndrome.

Whole exome sequencing identifies SCD5 as a novel causative gene for autosomal dominant nonsyndromic deafness

2020 ◽  
Vol 63 (5) ◽  
pp. 103855 ◽  
Author(s):  
Xingxing Lu ◽  
Yanmei Zhang ◽  
Li Chen ◽  
Qi Wang ◽  
Zhen'gang Zeng ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Nonsyndromic Deafness ◽  
Causative Gene ◽  
Whole Exome

scholarly journals Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Dong Wu ◽  
Dan Chen ◽  
Wen Shi ◽  
Wei Liu ◽  
Weixun Zhou ◽  
...  
Keyword(s):  
Blood Sample ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Tissue Sample ◽  
Protein Domain ◽  
Single Nucleotide Variants ◽  
Serrated Adenoma ◽  
Causative Gene ◽  
Multiple Sequence ◽  
Whole Exome

Background. Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. The present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA. Methods. DNA was extracted from the blood sample and tissue sample of SSA, followed by the whole exome sequencing (WES) analysis. Bioinformatics analysis was utilized to predict the deleteriousness of the identified variants. Multiple sequence alignment and conserved protein domain analyses were performed using online software. Sanger sequencing was used to validate the identified variants. Expression and diagnostic analysis of identified mutated genes was performed in the GSE119600 dataset (peripheral blood samples of PSC and UC) and GSE43841 dataset (tumor samples of SSA). Results. In the present study, a total of 842 single nucleotide variants (SNVs) in 728 genes were identified in the blood sample. Two variants, integrin beta 4 (ITGB4) (c.C2503G; p.P835A) and a mucin 3A (MUC3A) (c.C1019T; p.P340L), were further analyzed. MUC3A was associated with inflammatory bowel disease. Sanger sequence in blood revealed that the ITGB4 mutation was fully cosegregated with the result of WES in the patient. Additionally, a variant, tumor protein p53 gene (TP53) (c.86delA; p.N29Tfs ∗ 15) was identified in the tissue sample of SSA. Compared to that in normal controls, ITGB4 was upregulated in both UC and PSC, MUC3A was, respectively, upregulated and downregulated in PSC and UC, and TP53 was downregulated in SSA. ITGB4 and TP53 had a potential diagnostic value for UC, PSC and SSA. Conclusions. The present study demonstrated that the ITGB4 (c.C2503G; p.P835A) and MUC3A (c.C1019T; p.P340L) mutations may be the potential causative variants in a patient with UC associated with PSC and SSA. TP53 (c.86delA; p.N29Tfs ∗ 15) mutation may be associated with SSA in this patient.

scholarly journals Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene

2016 ◽  
Vol 19 (4) ◽  
pp. 412-420 ◽  
Author(s):  
Mir Reza Bekheirnia ◽  
Nasim Bekheirnia ◽  
Matthew N. Bainbridge ◽  
Shen Gu ◽  
Zeynep Hande Coban Akdemir ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Molecular Diagnosis ◽  
Congenital Anomalies ◽  
Causative Gene ◽  
Whole Exome

scholarly journals Whole-Exome Sequencing in 168 Korean Patients with Inherited Retinal Degeneration

2021 ◽  
Author(s):  
Dae Joong Ma ◽  
Hyun-Seob Lee ◽  
Kwangsoo Kim ◽  
Seongmin Choi ◽  
Insoon Jang ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Large Scale ◽  
Treatment Modalities ◽  
Macular Dystrophy ◽  
Genetic Profile ◽  
Molecular Testing ◽  
Causative Gene ◽  
Whole Exome

Abstract Background To date, no genetic analysis of inherited retinal disease (IRD) using whole-exome sequencing (WES) has been conducted in a large-scale Korean cohort. The aim of this study was to characterise the genetic profile of IRD patients in Korea using WES. Methods We performed comprehensive molecular testing in 168 unrelated Korean IRD patients using WES. The potential pathogenicity of candidate variants was assessed using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines, in silico prediction tools, published literature, and compatibility with known phenotypes or inheritance patterns.Results Causative variants were detected in 86/168 (51.2%) IRD patients, including 58/107 (54.2%) with retinitis pigmentosa, 7/15 (46.7%) with cone and cone-rod dystrophy, 2/3 (66.6%) with Usher syndrome, 1/2 (50.0%) with congenital stationary night blindness, 2/2 (100.0%) with Leber congenital amaurosis, 1/1 (100.0%) with Bietti crystalline dystrophy, 1/1 (100.0%) with Joubert syndrome, 9/10 (90.0%) with Stargardt macular dystrophy, 1/10 (10.0%) with vitelliform macular dystrophy, 1/11 (9.1%) with other forms of macular dystrophy, and 3/4 (75.0%) with choroideraemia. USH2A, ABCA4, and EYS were the most common causative genes associated with IRD. For retinitis pigmentosa, variants of USH2A and EYS were the most common causative gene mutations.Conclusions This study demonstrated the distribution of causative genetic mutations in Korean IRD patients. The data will serve as a reference for future genetic screening and development of treatment modalities for Korean IRD patients.

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