THU0466 Unraveling the Genetic Basis of Familial SAPHO Syndrome with Next-Generation Sequencing

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 344.3-344
Author(s):  
F.J. Del Castillo ◽  
T. Caniego ◽  
M. Hurtado-Nédélec ◽  
S. Chollet-Martín ◽  
E. Gόmez-Rosas ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Basis ◽  
Sapho Syndrome ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0143588 ◽  
Author(s):  
Patrícia B. S. Celestino-Soper ◽  
Anisiia Doytchinova ◽  
Hillel A. Steiner ◽  
Andrea Uradu ◽  
Ty C. Lynnes ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Basis ◽  
Familial Aggregation ◽  
Pacemaker Implantation ◽  
Next Generation ◽  
Generation Sequencing

Next-generation sequencing to identify candidate gene for hereditary mixed polyposis syndrome.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1515-1515
Author(s):  
Michele Caroline Gornick ◽  
Jun Li ◽  
Jishu Xu ◽  
Stephen B. Gruber
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Basis ◽  
Massively Parallel Sequencing ◽  
Low Frequency ◽  
Small Subset ◽  
Next Generation ◽  
Polyposis Syndrome ◽  
Candidate Locus ◽  
Increased Risk ◽  
Generation Sequencing

1515 Background: Rare monogenic disorders are often due to mutations that are highly penetrant, extremely rare, and strongly disrupt normal biology. Hereditary mixed polyposis syndrome (HMPS, OMIM ID %601228), is characterized by a mixture of atypical juvenile polyps, hyperplasic polyps, sessile serrated adenomas and an increased risk of colorectal cancer. Polyps appear to be inherited in an autosomal dominant fashion. The putative susceptibility locus initially mapped to 15q13-14, however, the genetic basis of this syndrome is not well understood, and no mutation or associated variants have been identified. Methods: Germline DNA from four individuals from a family with clinically and pathologically confirmed HMPS was subjected to massively parallel sequencing (Illumina GAII). Affected individuals had an average of 30x coverage of their exome and 10x coverage of their genome. Sequence calls were filtered using the criteria of ≥ 4x coverage, quality score over depth ≤ 50, depth of coverage ≤ 360, allele balance ≤ 0.75, number or MAPQ zero reads at locus < 4. Common variants were filtered out by excluding variants found in dbSNP (build131), 1000 Genomes Project, the Exome Variant Server or 80 unaffected controls sequenced by hybrid capture and whole exome sequencing. Polyphen2 and SIFT were used to predict pathogenicity of the novel, shared variants, and validated by Sanger sequencing. Expression levels of novel variants were examined in available tumor samples using qRT-PCR. Results: From the 32 previously unidentified nonsense, missense or splice site variants shared by the family members whose whole genomes were sequenced, only 5 (4 missense, 1 nonsense) were predicted to be damaging, leading to a small subset of novel candidate genes including ZNF426, which may be responsible for HMPS within this family. Conclusions: HMPS extremely difficult to accurately diagnosis and the genetic basis is unknown. Using next-generation sequencing we were able to detect previously unidentified low frequency allelic variants including a novel candidate locus.

scholarly journals Correction: Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147455
Author(s):  
Patrícia B. S. Celestino-Soper ◽  
Anisiia Doytchinova ◽  
Hillel A. Steiner ◽  
Andrea Uradu ◽  
Ty C. Lynnes ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Basis ◽  
Familial Aggregation ◽  
Pacemaker Implantation ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia

2021 ◽  
Vol 18 (16) ◽  
pp. 8520
Author(s):  
Aleksandra Klimkowicz-Mrowiec ◽  
Anna Dziubek ◽  
Małgorzata Sado ◽  
Marek Karpiński ◽  
Agnieszka Gorzkowska
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Analysis ◽  
Genetic Factor ◽  
Genetic Basis ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Clinical Syndrome ◽  
Next Generation ◽  
Early Onset Dementia ◽  
Generation Sequencing

The clinical manifestations of dementia are often rapidly matched to a specific clinical syndrome, but the underlying neuropathology is not always obvious. A genetic factor often plays an important role in early onset dementia, but there are cases in which the phenotype has a different genetic basis than is assumed. Two patients, at different times, presented to the Memory Clinic because of memory problems and difficulty in performing daily activities and work. Neither caregiver complained of marked behavioural or personality changes, except for apathy. Patients underwent standard dementia evaluation procedures including clinical symptoms, family history, neuroimaging, neuropsychological evaluation, and genetic analysis of selected genes. Based on specific clinical phenotypes and genetic analysis of selected genes, both patients were diagnosed with frontal variant of Alzheimer’s disease. The presence of a rare polymorphism in PSEN2 in both patients allowed the discovery that they belong to the same family. This fact reinforced the belief that there is a strong genetic factor responsible for causing dementia in the family. Next-generation sequencing based on a panel of 118 genes was performed to identify other potential genetic factors that may determine the background of the disease. A mutation in the GRN gene was identified, and the previous diagnosis was changed to frontotemporal dementia. The described cases show how important it is to combine all diagnostic tests available in the diagnostic centre, including new generation genetic tests, in order to establish/confirm the pathological background of clinical symptoms of dementia. If there is any doubt about the final diagnosis, persistent efforts should be made to verify the cause.

Abstract 050: Mutational Spectrum in a Cohort of Chinese Sporadic Dilated Cardiomyopathy by Next-generation Sequencing

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Lei Xu ◽  
Aijun Sun ◽  
Yunzeng Zou ◽  
Kai Hu ◽  
Zheng Fan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Dilated Cardiomyopathy ◽  
Genetic Basis ◽  
Next Generation ◽  
Genetic Studies ◽  
1000 Genomes ◽  
Mutational Screening ◽  
The Mean ◽  
Mutant Genes ◽  
Generation Sequencing

Rationale: Dilated cardiomyopathy (DCM) is a leading cause of heart failure and have a genetic basis in 20-30% of cases. Genetic studies in familial DCM have found mutations identified in more than 30 genes. However, the genetics of sporadic DCM is still unknown. Objective: To provide new insights into the pathophysiology of sporadic DCM, a mutational screening on 30 DCM-causing genes in a cohort was performed. Methods and Results: Patients diagnosed with idiopathic DCM were recruited into the study and underwent clinical evaluation. Genomic DNA was isolated from the peripheral blood and then 30 genes ( ACTC, DES, SGCD, MYH7, TNNT2, TPM1, TTN, VCL, MYBPC3, CSRP3, ACTN2, PLN, LDB3, MYH6, ABCC9, TNNC1, TCAP, TNNI3, EYA4, TMPO, PSEN1/2, CRYAB, PDLIM3, MYPN, LAMA4, ILK, ANKRD1, RBM20, LMNA , and SCN5A ) of every sample were detected by next-generation sequencing. All called variants were compared against National Center for Biotechnology Information SNP Database build 137 and the March 2012 release of the 1000 Genomes project. All variants identified in the cohort were compared in ethnic-matched controls consisting of 197 adult Chinese from the 1000 Genomes. The pathogenicity of the variants absent from controls were evaluated by SIFT software. Sixty-six adult Chinese unrelated DCM patients were tested for up to 30 genes causing familial DCM. The mean age was 49.14±15.97 years. Every patient was detected nonsynonymous variants, and the total 87 variants were composed of 39 novel and 48 known. Among the whole 87 variants, 34 satisfied the criteria (1) absent from ethnic-matched controls and (2) altering evolutionary conservation of amino acid verified by SIFT analysis, which were considered pathogenic mutations, identified in 30 patients accounting for 45.45% of the cohort. The 2 most frequent genes involved in mutation positive patients were SCN5A (12.12%) and MYH7 (10.61%). Conclusions: Mutant genes found in familial DCM were also common in sporadic DCM, and the discovery of novel mutations spanned the spectrum of DCM genetics, implicating that genetic etiologies play an important role in pathogenesis of sporadic DCM.

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