Exome Sequencing
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2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Yue Zhang ◽  
Manhong Xu ◽  
Minglian Zhang ◽  
Guoxing Yang ◽  
Xiaorong Li

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.


2021 ◽  
Author(s):  
Bum-Sup Jang ◽  
In Ah Kim

Aim: We tested whether machine-learning algorithm could find biomarkers predicting overall survival in breast cancer patients using blood-based whole-exome sequencing data. Materials & methods: Whole-exome sequencing data derived from 1181 female breast cancer patients within the UK Biobank was collected. We found feature genes (n = 50) regarding total mutation burden using the long short-term memory model. Then, we developed the XGBoost survival model with selected feature genes. Results: The XGBoost survival model performed acceptably, with a concordance index of 0.75 and a scaled Brier score of 0.146 in terms of overall survival prediction. The high-mutation group exhibited inferior overall survival compared with the low-mutation group in patients ≥56 years (log-rank test, p = 0.042). Conclusion: We showed that machine-learning algorithms can be used to predict overall survival in breast cancer patients from blood-based whole-exome sequencing data.


Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1618
Author(s):  
Olga Shatokhina ◽  
Natalia Semenova ◽  
Nina Demina ◽  
Elena Dadali ◽  
Alexander Polyakov ◽  
...  

Here, we report a novel truncating mutation in the ubiquitin-specific peptidase gene (USP53) causing low-γ-GT (GGT) cholestasis. Genetic testing was carried out, including clinical exome sequencing for the proband and Sanger sequencing for the proband and his parents. The proband harbored a novel c.1017_1057del (p.(Cys339TrpfsTer7)) mutation in the ubiquitin carboxyl-terminal hydrolase (UCH) domain of USP53; we describe the clinical and laboratory features of the patient with a rare type of low-GGT cholestasis caused by this variant. The clinical presentation was found to be similar to that of phenotypes described in previous studies. However, there was an unusual presence of liver hemangiomas observed in our patient. Thus, our report reinforces the link between USP53 mutations and cholestasis. With this report, we confirm USP53 as the gene for low-GGT cholestasis and describe liver hemangiomas as a possible additional symptom of the phenotype spectrum. The inclusion of USP53 in the OMIM database and liver gene panels can further increase the effectiveness of molecular genetic studies.


2021 ◽  
Vol 15 ◽  
Author(s):  
Anna Macias ◽  
Jakub Piotr Fichna ◽  
Malgorzata Topolewska ◽  
Maria J. Rȩdowicz ◽  
Anna M. Kaminska ◽  
...  

Limb–girdle muscular dystrophy type R1 (LGMDR1) is caused by mutations in CAPN3 and is the most common type of recessive LGMD. Even with the use of whole-exome sequencing (WES), only one mutant allele of CAPN3 is found in a significant number of LGMDR patients. This points to a role of non-coding, intronic or regulatory, sequence variants in the disease pathogenesis. Targeted sequencing of the whole CAPN3 gene including not only intronic, 3′ and 5′ UTRs but also potential regulatory regions was performed in 27 patients suspected with LGMDR1. This group included 13 patients with only one mutated CAPN3 allele detected previously with exome sequencing. A second rare variant in the non-coding part of CAPN3 was found in 11 of 13 patients with previously identified single mutation. Intronic mutations were found in 10 cases, with c.1746-20C>G variant present in seven patients. In addition, a large deletion of exons 2–8 was found in one patient. In the patients with no causative mutation previously found, we detected rare CAPN3 variants in 5 out of 10 patients and in two of them in a compound heterozygous state. Rare variants within putative regulatory sequences distant from the CAPN3 gene were found in 15 patients, although in 11 of these cases, other variants are deemed causative. The results indicate that intronic mutations are common in Polish LGMDR patients, and testing for non-coding mutations in CAPN3 should be performed in apparently single heterozygous patients.


2021 ◽  
Vol 13 (615) ◽  

2021 ◽  
Author(s):  
Mirjam Plantinga ◽  
Lauren Zwienenberg ◽  
Eva Dijk ◽  
Hanna Breet ◽  
Janouk Diphoorn ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Ma ◽  
Aping Sun ◽  
Yingshuang Zhang ◽  
Dongsheng Fan ◽  
Xiaoxuan Liu

Introduction: Charcot–Marie–Tooth disease type 2A (CMT2A) is a group of clinically and genetically heterogeneous disorders, which is mostly caused by mutations of the mitofusin2 (MFN2) gene. As the genotype–phenotype characteristics of CMT2A were still incompletely understood, we further explored the spectrum of CMT2A variants in China and demonstrated their phenotypic diversities.Methods: A total of 402 index patients/families with CMT throughout Mainland China were enrolled in this study. Among them, we analyzed 20 unrelated index cases with CMT2A by Sanger sequencing, next-generation sequencing, or whole-exome sequencing. Detailed clinical and genetic features of CMT2A patients were collected and analyzed. Of note, de novo mutations were not rare in MFN2 gene; we compared the clinical features of patients from the de novo group with those from the non-de novo group.Results: We identified 20 MFN2 variants, occupying 5.0% of CMT. Most patients presented with early onset and moderate phenotype with abnormal gait and foot drop as the main complaints at onset. Pyramidal signs accounts for 31.6% (6/19) in all patients, which is not uncommon. Four novel variants (p.Tyr752*, c.475-2A>G, p.Val99Met, and p.Arg275_Gln276insArg) were identified in the cohort. Besides, de novo variants occupied 35.0% (7/20) in our study with a much earlier age at onset compared with those in the non-de novo group (p = 0.021).Conclusion: Chinese CMT2A is a predominant typical pure CMT2A, with early onset and mild to moderate phenotype. Given the high frequency of de novo MFN2 mutations, genetic study should be considered for patients with early onset and severe idiopathic axonal neuropathy.


Author(s):  
Pouria Mohammadi ◽  
Elham Salehi Siavashani ◽  
Mohammad Farid Mohammadi ◽  
Afshin Bahramy ◽  
Navid Almadani ◽  
...  

2021 ◽  
Author(s):  
Rui Zhang ◽  
Yajing Hao ◽  
Ying Xu ◽  
Jiale Qin ◽  
Yanfang Wang ◽  
...  

Abstract Background: Isolated sulfite oxidase deficiency (ISOD) is the rarest types of life-threatening neurometabolic disorders characterized by neonatal intractable seizures and severe developmental delay with an autosomal recessive mode of inheritance. ISOD is extremely rare and till date only 32 mutations have been identified and reported worldwide. Germline mutation in SUOX gene causes ISOD. Methods: Here, we investigated a 5-days old Chinese female child, presented with intermittent tremor or seizures of limbs, neonatal encephalopathy, subarachnoid cyst and haemorrhage, dysplasia of corpus callosum, neonatal convulsion, respiratory failure, cardiac failure, hyperlactatemia, severe metabolic acidosis, hyperglycemia, hyperkalemia, moderate anemia, atrioventricular block and complete right bundle branch block. Results: Whole exome sequencing identified a novel homozygous transition (c.1227G>A) in exon 6 of the SUOX gene in the proband. This novel homozygous variant leads to the formation of a truncated sulfite oxidase (p.Trp409*) of 408 amino acids. Hence, it is a loss-of-function variant. Proband’s father and mother is carrying this novel variant in a heterozygous state. This variant was not identified in 200 ethnically matched normal healthy control individuals. Conclusions: Our study not only expand the mutational spectrum of SUOX gene associated ISOD, but also strongly suggested the application of whole exome sequencing for identifying candidate genes and novel disease-causing mutations.


2021 ◽  
Vol 22 (20) ◽  
pp. 11007
Author(s):  
Dżamila M. Bogusławska ◽  
Michał Skulski ◽  
Beata Machnicka ◽  
Stanisław Potoczek ◽  
Sebastian Kraszewski ◽  
...  

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.


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