scholarly journals Whole exome-trio analysis reveals rare variants associated with Congenital Pouch Colon

2019 ◽  
Author(s):  
Sonal Gupta ◽  
Praveen Mathur ◽  
Ashwani Kumar Mishra ◽  
Krishna Mohan Medicherla ◽  
Prashanth Suravajhala
Keyword(s):  
Rare Variants ◽  
De Novo ◽  
Anorectal Malformations ◽  
Open Reading Frames ◽  
Missense Mutations ◽  
Clinical Genetic ◽  
Variants Of Unknown Significance ◽  
Whole Exome ◽  
Congenital Pouch Colon ◽  
Pouch Colon

AbstractAnorectal malformations (ARM) are individually common but Congenital Pouch Colon (CPC), a rare anorectal anomaly causes a dilated pouch in genitourinary tract. We have earlier attempted to understand the clinical genetic makeup of CPC and identified genes responsible for the disease using whole exome sequencing (WES). Here we report our studies of CPC, by identifying de novo heterozygous missense mutations in 16 proband-parent trios and further discover variants of unknown significance which could provide insights into CPC manifestation and its etiology. Our study confirms candidate mutations in genes, viz. C7orf57, C10orf120, C9orf84 and MUC16, CTC1 particularly emphasizing the role of hypothetical genes or open reading frames causing this developmental disorder. Variant validation revealed disease causing mutations associated with CPC and genitourinary diseases which could close the gaps of surgery in bringing intervention in therapies.

scholarly journals Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 95 ◽  
Author(s):  
Sonal Gupta ◽  
Nidhi Gupta ◽  
Pradeep Tiwari ◽  
Saji Menon ◽  
Praveen Mathur ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Rare Variants ◽  
Clinical Genetic ◽  
Northwestern India ◽  
Whole Exome ◽  
Congenital Pouch Colon ◽  
Pouch Colon ◽  
Non Coding Rnas ◽  
Polymerase Chain

Congenital Pouch Colon (CPC) is a rare anorectal anomaly common to northwestern India, specifically Rajasthan. Despite efforts to understand the clinical genetic makeup of CPC, no attempt on identifying non-coding RNAs was done. We have earlier reported CPC’s rare variants from whole exome sequencing (WES) across 18 affected samples in a total of 64 subjects. A Smith–Waterman algorithm was used to infer a couple of lncRNAs from WES samples of CPC with predictions from the Noncode database. Further screening and quantification using polymerase chain reaction (PCR), we ascertained interactions using Micro Scale Thermophoresis (MST). We report the role of lnc-EPB41-1-1 shown to be promiscuously interacting with KIF13A substantiating their role in regulation.

scholarly journals lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

2018 ◽  
Author(s):  
Sonal Gupta ◽  
Nidhi Gupta ◽  
Pradeep Tiwari ◽  
Saji Menon ◽  
Praveen Mathur ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Rare Variants ◽  
Western India ◽  
Clinical Genetic ◽  
Whole Exome ◽  
Congenital Pouch Colon ◽  
Pouch Colon ◽  
Non Coding Rnas ◽  
North Western

Congenital Pouch Colon (CPC) is a rare anorectal anomaly common to North Western India specifically Rajasthan. Despite efforts to understand the clinical genetic makeup of CPC, no attempt on identifying non-coding RNAs was done. We have earlier reported CPC's rare variants from whole exome sequencing across 18 affected samples in a total of 64 subjects. A Smith-Waterman algorithm was used to infer a couple of lncRNAs from WES samples of CPC with predictions from the Noncode database. Further screening and quantification using PCR, we ascertained interactions using Micro Scale Thermophoresis (MST). We report the role of lnc-EPB41-1-1 shown to be promiscuously interacting with KIF13A substantiating their role in regulation.

scholarly journals Author Correction: Whole exome sequencing reveals rare variants linked to congenital pouch colon

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Praveen Mathur ◽  
Krishna Mohan Medicherla ◽  
Spandan Chaudhary ◽  
Mruduka Patel ◽  
Prashanth Bagali ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variants ◽  
Whole Exome ◽  
Congenital Pouch Colon ◽  
Pouch Colon

scholarly journals Application of Whole Exome-Trio Analysis Reveals Rare Variants Associated with Congenital Pouch Colon

2022 ◽  
Author(s):  
Sonal Gupta ◽  
Praveen Mathur ◽  
Ashwani Kumar Mishra ◽  
Krishna Mohan Medicherla ◽  
Obul Reddy Bandapalli ◽  
...  
Keyword(s):  
Rare Variants ◽  
Whole Exome ◽  
Congenital Pouch Colon ◽  
Pouch Colon

scholarly journals Whole exome sequencing reveals rare variants linked to congenital pouch colon

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Praveen Mathur ◽  
Krishna Mohan Medicherla ◽  
Spandan Chaudhary ◽  
Mruduka Patel ◽  
Prashanth Bagali ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variants ◽  
Whole Exome ◽  
Congenital Pouch Colon ◽  
Pouch Colon

An intronic variant disrupts mRNA splicing and causes FGFR3-related skeletal dysplasia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ting Xu ◽  
Liang Shi ◽  
Weiqian Dai ◽  
Xuefan Gu ◽  
Yongguo Yu ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Findings ◽  
Recurrent Mutation ◽  
Mrna Splicing ◽  
Additional Patient ◽  
Missense Mutations ◽  
Splicing Variant ◽  
Amino Acid Insertion ◽  
Whole Exome ◽  
Minigene Assay

Abstract Objectives Achondroplasia and hypochondroplasia are the most common forms of disproportionate short stature, of which the vast majority of cases can be attributed to the hotspot missense mutations in the gene FGFR3. Here we presented cases with a novel cryptic splicing variant of FGFR3 gene and aimed to interrogate the variant pathogenicity. Case presentaiton In whole exome sequencing of two patients with hypochondroplasia-like features, a de novo intronic variant c.1075 + 95C>G was identified, predicted to alter mRNA splicing. Minigene assay showed that this intronic variant caused retention of a 90-nucleotide segment of intron 8 in mRNA, resulting in a 30-amino acid insertion at the extracellular domain of the protein. This is the first likely pathogenic splicing variant identified in the FGFR3 gene and was detected in one additional patient among 26 genetically unresolved patients. Conclustions Our results strongly suggest that c.1075 + 95C>G is a recurrent mutation and should be included in genetic testing of FGFR3 especially for those patients with equivocal clinical findings and no exonic mutations identified.

Whole‐Exome Sequencing of a Saudi Epilepsy Cohort Reveals Association Signals in Known and Potentially Novel Loci

2021 ◽  
Author(s):  
Amein Kadhem AlAli ◽  
Abdulrahman Al-Enazi ◽  
Ahmed Ammar ◽  
Mahmoud Hajj ◽  
Cyril Cyrus ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variants ◽  
High Rate ◽  
Variants Of Unknown Significance ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Novel Variants ◽  
Unknown Significance ◽  
Rare Genetic Variants

Abstract Background Epilepsy, a serious chronic neurological condition effecting up to 100 million people globally, has clear genetic underpinnings including common and rare variants. In Saudi Arabia the prevalence of epilepsy is high and caused mainly by perinatal and genetic factors. No whole-exome sequencing (WES) studies have been performed to date in Saudi Arabian Epilepsy cohorts. This offers a unique opportunity for the discovery of rare genetic variants impacting this disease as there is a high rate of consanguinity amongst large tribal pedigrees. Results We performed WES on 144 individuals diagnosed with epilepsy, to interrogate known Epilepsy related genes for known and functional novel variants. We also used an American College of Medical Genetics (ACMG) guideline based variant prioritization approach in an attempt to discover putative causative variants. We identified a 32 potentially causative pathogenic variants across 30 different genes in 44/144 (30%) of these Saudi Epilepsy individuals. We also identified 232 variants of unknown significance (VUS) across 101 different genes in 133/144 (92%) subjects. Strong enrichment of variants of likely pathogenicity were observed in previously described epilepsy-associated loci, and a number of putative pathogenic variants in novel loci are also observed. Conclusion Several putative pathogenic variants known to be epilepsy-related loci were identified for the first time in our population, in addition to several potential new loci have been identified which may be prioritized for further investigation.

scholarly journals Nearly Half of TP53 Germline Variants Predicted To Be Pathogenic in Patients With Osteosarcoma Are De Novo: A Report From the Children’s Oncology Group

2020 ◽  
pp. 1187-1195
Author(s):  
Brandon J. Diessner ◽  
Nathan Pankratz ◽  
Anthony J. Hooten ◽  
Lisa Mirabello ◽  
Aaron L. Sarver ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Rare Variants ◽  
De Novo ◽  
Phase 1 ◽  
Control Measures ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Whole Exome ◽  
History Of ◽  
De Novo Variant

PURPOSE To ascertain the prevalence of recurrent de novo variants among 240 pediatric patients with osteosarcoma (OS; age < 20 years) unselected for family history of cancer. METHODS The identification of de novo variants was implemented in 2 phases. In the first, we identified genes with a rare (minor allele frequency < 0.01) de novo variant in > 1 of the 95 case-parent trios examined by whole-exome sequencing (WES) who passed quality control measures. In phase 2, 145 additional patients with OS were evaluated by targeted sequencing to identify rare de novo variants in genes nominated from phase 1. Recurrent rare variants identified from phase 1 and 2 were verified as either de novo or inherited by Sanger sequencing of affected patients and their parents. Categorical and continuous data were analyzed using Fisher exact test and t tests, respectively. RESULTS Among 95 case-parent trios who underwent WES, we observed 61 de novo variants in 60 genes among 47 patients, with TP53 identified as the only gene with a pathogenic or likely pathogenic (P/LP) de novo variant in more than one case-parent trio. Among all 240 patients with OS, 13 (5.4%) harbored a P/LP TP53 germline variant, of which 6 (46.2%) were confirmed to be de novo. CONCLUSION Apart from TP53, we did not observe any other recurrent de novo P/LP variants in the case-parent trios, suggesting that new mutations in other genes are not a frequent cause of pediatric OS. That nearly half of P/LP TP53 variants in our sample were de novo suggests universal screening for germline TP53 P/LP variants among pediatric patients with OS should be considered.

scholarly journals Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations – A case report

2019 ◽  
Author(s):  
Sofia Thunström ◽  
Markus Axelsson
Keyword(s):  
Case Report ◽  
Peripheral Neuropathy ◽  
De Novo ◽  
Age Of Onset ◽  
De Novo Mutation ◽  
Missense Mutations ◽  
Dural Ectasia ◽  
Whole Exome ◽  
Demyelinating Peripheral Neuropathy ◽  
Multiple Cysts

Abstract Background: Missense mutations in SAMD9L gene is associated with ataxia-pancytopenia syndrome (ATXPC), OMIM#159550. Common clinical features in these patients include neurological and hematological symptoms. The phenotype and age of onset is variable. Case Presentation: In this case report whole exome sequencing (WES) revealed a not previously reported de novo variant c.2686T>G, p.(Phe896Val) in SAMD9L in a patient with widespread findings of slow developing pathology in the peripheral and central nervous system. The clinical picture was dominated by neurological symptoms, unlike previously described cases, and in addition dural ectasias and multiple cysts in the brain was observed using magnetic resonance imaging. Conclusions: This case underscores the effect of variable expressivity, i.e. different mutations in the same gene can cause different phenotypes. Keywords: Leukoencephalopathia, demyelinating peripheral neuropathy, dural ectasia explained, de novo mutation, the SAMD9L gene.

Sign in / Sign up

Export Citation Format

Share Document