scholarly journals NGS Gene Panel Analysis Revealed Novel Mutations in Patients with Rare Congenital Diarrheal Disorders

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 262
Author(s):  
Maria Valeria Esposito ◽  
Marika Comegna ◽  
Gustavo Cernera ◽  
Monica Gelzo ◽  
Lorella Paparo ◽  
...  
Keyword(s):  
Clinical Picture ◽  
Autosomal Recessive ◽  
Disease Gene ◽  
Rapid Diagnosis ◽  
Novel Mutations ◽  
Bioinformatic Tools ◽  
Congenital Chloride Diarrhea ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Microvillous Inclusion Disease

Congenital diarrheal disorders (CDDs) are early-onset enteropathies generally inherited as autosomal recessive traits. Most patients with CDDs require rapid diagnosis as they need immediate and specific therapy to avoid a poor prognosis, but their clinical picture is often overlapping with a myriad of nongenetic diarrheal diseases. We developed a next-generation sequencing (NGS) panel for the analysis of 92 CDD-related genes, by which we analyzed patients suspect for CDD, among which were (i) three patients with sucrose-isomaltase deficiency; (ii) four patients with microvillous inclusion disease; (iii) five patients with congenital tufting enteropathy; (iv) eight patients with glucose-galactose malabsorption; (v) five patients with congenital chloride diarrhea. In all cases, we identified the mutations in the disease-gene, among which were several novel mutations for which we defined pathogenicity using a combination of bioinformatic tools. Although CDDs are rare, all together, they have an incidence of about 1%. Considering that the clinical picture of these disorders is often confusing, a CDD-related multigene NGS panel contributes to unequivocal and rapid diagnosis, which also reduces the need for invasive procedures.

scholarly journals Ataxia with Oculomotor Apraxia Type 4 with PNKP Common “Portuguese” and Novel Mutations in Two Belarusian Families

2019 ◽  
Vol 08 (02) ◽  
pp. 058-062
Author(s):  
Galina Rudenskaya ◽  
Andrey Marakhonov ◽  
Olga Shchagina ◽  
Ekaterina Lozier ◽  
Elena Dadali ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Developmental Delay ◽  
Autosomal Recessive ◽  
Novel Mutations ◽  
Related Disorder ◽  
Oculomotor Apraxia ◽  
Biallelic Mutations ◽  
Next Generation Sequencing Ngs ◽  
Ataxia With Oculomotor Apraxia ◽  
Generation Sequencing

AbstractAtaxia with oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive, PNKP-related disorder delineated in 2015 in Portugal. We diagnosed AOA4 by next generation sequencing (NGS) followed by Sanger's sequencing in three boys from two unrelated Belarusian families. In both families, one of the heterozygous PNKP mutations was c.1123G>T, common in Portuguese patients; biallelic mutations, c.1270_1283dup14 and c.1029+2T>C, respectively, were novel. These are the first reported AOA4 Slavic cases and the first with a “Portuguese” PNKP mutation outside Portugal. Distinction in two brothers was microcephaly but their disease was not severe in contrast to PNKP-related “microcephaly, seizures, and developmental delay” and reported cases with features of both phenotypes.

scholarly journals Targeted Next-Generation Sequencing of a Deafness Gene Panel (MiamiOtoGenes) Analysis in Families Unsuitable for Linkage Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Haiqiong Shang ◽  
Denise Yan ◽  
Naeimeh Tayebi ◽  
Kolsoum Saeidi ◽  
Afsaneh Sahebalzamani ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Linkage Analysis ◽  
Autosomal Recessive ◽  
Target Sequence ◽  
Novel Mutations ◽  
Nonsyndromic Deafness ◽  
Targeted Next Generation Sequencing ◽  
Deafness Gene ◽  
Comprehensive Diagnosis ◽  
Generation Sequencing

Hearing loss (HL) is a common sensory disorder in humans with high genetic heterogeneity. To date, over 145 loci have been identified to cause nonsyndromic deafness. Furthermore, there are countless families unsuitable for the conventional linkage analysis. In the present study, we used a custom capture panel (MiamiOtoGenes) to target sequence 180 deafness-associated genes in 5 GJB2 negative deaf probands with autosomal recessive nonsyndromic HL from Iran. In these 5 families, we detected one reported and six novel mutations in 5 different deafness autosomal recessive (DFNB) genes (TRIOBP, LHFPL5, CDH23, PCDH15, and MYO7A). The custom capture panel in our study provided an efficient and comprehensive diagnosis for known deafness genes in small families.

scholarly journals Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Oyediran Akinrinade ◽  
Tiina Heliö ◽  
Ronald H. Lekanne Deprez ◽  
Jan D. H. Jongbloed ◽  
Ludolf G. Boven ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Human Disease ◽  
Disease Gene ◽  
Reference Population ◽  
Population Database ◽  
Missense Variants ◽  
Clinical Diagnostic ◽  
Significant Enrichment ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Recent advancements in next generation sequencing (NGS) technology have led to the identification of the giant sarcomere gene, titin (TTN), as a major human disease gene. Truncating variants of TTN (TTNtv) especially in the A-band region account for 20% of dilated cardiomyopathy (DCM) cases. Much attention has been focused on assessment and interpretation of TTNtv in human disease; however, missense and non-frameshifting insertions/deletions (NFS-INDELs) are difficult to assess and interpret in clinical diagnostic workflow. Targeted sequencing covering all exons of TTN was performed on a cohort of 530 primary DCM patients from three cardiogenetic centres across Europe. Using stringent bioinformatic filtering, twenty-nine and two rare TTN missense and NFS-INDELs variants predicted deleterious were identified in 6.98% and 0.38% of DCM patients, respectively. However, when compared with those identified in the largest available reference population database, no significant enrichment of such variants was identified in DCM patients. Moreover, DCM patients and reference individuals had comparable frequencies of splice-region missense variants with predicted splicing alteration. DCM patients and reference populations had comparable frequencies of rare predicted deleterious TTN missense variants including splice-region missense variants suggesting that these variants are not independently causative for DCM. Hence, these variants should be classified as likely benign in the clinical diagnostic workflow, although a modifier effect cannot be excluded at this stage.

scholarly journals Next Generation Sequencing Identifies Five Novel Mutations in Lebanese Patients with Bardet–Biedl and Usher Syndromes

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1047 ◽  
Author(s):  
Lama Jaffal ◽  
Wissam H Joumaa ◽  
Alexandre Assi ◽  
Charles Helou ◽  
George Cherfan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Usher Syndrome ◽  
Bioinformatic Analysis ◽  
Next Generation ◽  
Novel Mutations ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Aim: To identify disease-causing mutations in four Lebanese families: three families with Bardet–Biedl and one family with Usher syndrome (BBS and USH respectively), using next generation sequencing (NGS). Methods: We applied targeted NGS in two families and whole exome sequencing (WES) in two other families. Pathogenicity of candidate mutations was evaluated according to frequency, conservation, in silico prediction tools, segregation with disease, and compatibility with inheritance pattern. The presence of pathogenic variants was confirmed via Sanger sequencing followed by segregation analysis. Results: Most likely disease-causing mutations were identified in all included patients. In BBS patients, we found (M1): c.2258A > T, p. (Glu753Val) in BBS9, (M2): c.68T > C; p. (Leu23Pro) in ARL6, (M3): c.265_266delTT; p. (Leu89Valfs*11) and (M4): c.880T > G; p. (Tyr294Asp) in BBS12. A previously known variant (M5): c.551A > G; p. (Asp184Ser) was also detected in BBS5. In the USH patient, we found (M6): c.188A > C, p. (Tyr63Ser) in CLRN1. M2, M3, M4, and M6 were novel. All of the candidate mutations were shown to be likely disease-causing through our bioinformatic analysis. They also segregated with the corresponding phenotype in available family members. Conclusion: This study expanded the mutational spectrum and showed the genetic diversity of BBS and USH. It also spotlighted the efficiency of NGS techniques in revealing mutations underlying clinically and genetically heterogeneous disorders.

Novel mutations in sporadic typical carcinoids of the lung (lung-TC): Tumor genomic profile by next generation sequencing (NGS).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 11596-11596
Author(s):  
Ivana GABRIELA Sullivan ◽  
Ludovic Lacroix ◽  
Julien Adam ◽  
Aurelie Honore ◽  
Nicolas Dorvault ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genomic Profile ◽  
Next Generation ◽  
Novel Mutations ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals Cone Dystrophy in Patient with HomozygousRP1L1Mutation

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sachiko Kikuchi ◽  
Shuhei Kameya ◽  
Kiyoko Gocho ◽  
Said El Shamieh ◽  
Keiichiro Akeo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cone Dystrophy ◽  
Homozygous Mutation ◽  
Full Field ◽  
Clinical Evaluations ◽  
Normal Visual Acuity ◽  
Severe Reduction ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Cone Density

The purpose of this study was to determine whether an autosomal recessive cone dystrophy was caused by a homozygousRP1L1mutation. A family including one subject affected with cone dystrophy and four unaffected members without evidence of consanguinity underwent detailed ophthalmic evaluations. The ellipsoid and interdigitation zones on the spectral-domain optical coherence tomography images were disorganized in the proband. The proband had a reduced amplitude of cone and flicker full-field electroretinograms (ERGs). Focal macular ERGs and multifocal ERGs were severely reduced in the proband. A homozygousRP1L1mutation (c.3628T>C, p.S1210P) was identified in the proband. Family members who were heterozygous for the p.S1210P mutation had normal visual acuity and normal results of clinical evaluations. To investigate other putative pathogenic variant(s), a next-generation sequencing (NGS) approach was applied to the proband. NGS identified missense changes in the heterozygous state of thePCDH15,RPGRIP1, andGPR98genes. None of these variants cosegregated with the phenotype and were predicted to be benign reinforcing the putative pathogenicity of theRP1L1homozygous mutation. The AO images showed a severe reduction of the cone density in the proband. Our findings indicate that a homozygous p.S1210P exchange in theRP1L1gene can cause cone dystrophy.

scholarly journals sgDI-tector: defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs

2021 ◽  
Author(s):  
Andrea Di Gioacchino ◽  
Rachel Legendre ◽  
Yannis Rahou ◽  
Valerie Najburg ◽  
Pierre Charneau ◽  
...  
Keyword(s):  
Regulatory Sequences ◽  
Accessory Proteins ◽  
Viral Genomes ◽  
Bioinformatic Tools ◽  
Subgenomic Rnas ◽  
Next Generation Sequencing Ngs ◽  
User Friendly ◽  
Ngs Data ◽  
Initial Knowledge ◽  
Generation Sequencing

Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. sgDI-tector allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. We produced NGS data and successfully detected the nested set of sgRNAs with the ranking M>ORF3a>N>ORF6>ORF7a>ORF8>S>E>ORF7b. We also compared the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.

scholarly journals Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1467
Author(s):  
Gema García-García ◽  
Alba Berzal-Serrano ◽  
Piedad García-Díaz ◽  
Rebeca Villanova-Aparisi ◽  
Sara Juárez-Rodríguez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Targeted Ngs ◽  
Syndromic Hearing Loss ◽  
Genetics And Genomics ◽  
Custom Panel ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogenic variants in 26 different genes, 15 with AR inheritance pattern, 9 with AD and 2 that are X-linked. Fourteen of the found variants are novel. This study highlights the clinical utility of targeted NGS for sensorineural hearing loss. The optimal panel for HL must be designed according to the spectrum of the most represented genes in a given population and the laboratory capabilities considering the pressure on healthcare.

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