Objectives: Copy-number variations (CNVs) are large-scale deletions or duplications of DNA that have required specialized detection methods, such as microarray-based genomic hybridization or multiplex ligation probe amplification. However, recent advances in bioinformatics have made it possible to detect CNVs from next-generation DNA sequencing (NGS) data. Maturity-onset diabetes of the young (MODY) 5 is a subtype of autosomal-dominant diabetes that is often caused by heterozygous deletions involving the HNF1B gene on chromosome 17q12. We evaluated the utility of bioinformatic processing of raw NGS data to detect chromosome 17q12 deletions in MODY5 patients.
Methods: NGS data from 57 patients clinically suspected to have MODY but who were negative for pathogenic mutations using a targeted panel were re-examined using a CNV calling tool (CNV Caller, VarSeq version 1.4.3). Potential CNVs for MODY5 were then confirmed using whole-exome sequencing, cytogenetic analysis and breakpoint analysis when possible.
Results: Whole-gene deletions in HNF1B, ranging from 1.46 to 1.85 million basepairs in size, were detected in 3 individuals with features of MODY5. These were confirmed by independent methods to be part of a more extensive 17q12 deletion syndrome. Two additional patients carrying a 17q12 deletion were subsequently diagnosed using this method.
Conclusions: Large-scale deletions are the most common cause of MODY5 and can be detected directly from NGS data, without the need for additional methods.
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http://dx.doi.org/10.1016/j.jcjd.2020.06.001 | DOI Listing |
Eur J Pediatr
December 2024
Department of Medical Genetics, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.
Unlabelled: The RASopathies are a group of disorders resulting from a germline variant in the genes encoding the Ras/mitogen-activated protein kinase pathway. These disorders include Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), Costello syndrome (CS), Legius syndrome (LS), and neurofibromatosis type 1 (NF1), and have overlapping clinical features due to RAS/MAPK dysfunction. In this study, we aimed to describe the clinical and molecular features of patients exhibiting phenotypic manifestations consistent with RASopathies.
View Article and Find Full Text PDFGene
December 2024
Department of Molecular Biology and Biotechnology, Cotton University, Panbazar, Guwahati, Assam 781001, India. Electronic address:
In recent years, third-generation sequencing (TGS) technologies have transformed genomics and transcriptomics research, providing novel opportunities for significant discoveries. The long-read sequencing platforms, with their unique advantages over next-generation sequencing (NGS), including a definitive protocol, reduced operational time, and real-time sequencing, possess the potential to transform plant genomics. TGS optimizes and enhances the efficiency of data analysis by removing the necessity for time-consuming assembly tools.
View Article and Find Full Text PDFArch Pathol Lab Med
December 2024
From the Departments of Pathology, University of Michigan Medical School, Ann Arbor (Plotzke, Manthei, Fullen, Chan, Bresler, Xiao, Andea, Harms).
Context.—: Patients with melanoma can develop second tumors representing either metastases or new primary melanoma. This distinction has profound implications for management.
View Article and Find Full Text PDFJ Assist Reprod Genet
December 2024
Department of Reproductive Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Purpose: This study aimed to investigate the genetic etiology in an infertile patient presenting with consistently elevated progesterone levels.
Methods: Genomic DNA was extracted from the patient's blood sample and subjected to whole-genome sequencing (NGS) using the Illumina NovaSeq platform. Bioinformatic analyses were conducted to identify single nucleotide variants (SNVs) and insertion-deletion mutations (Indels) potentially associated with the patient's clinical phenotype.
Oncologist
December 2024
Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, United States.
Background: Sarcomatoid carcinomas (SC) are rare tumors with both epithelial and mesenchymal characteristics, linked to aggressive behavior and poor prognosis. Sarcomatoid carcinoma of unknown primary (SCUP) is an exceedingly rare subset with limited literature and no standardized management guidelines. This study aims to characterize the clinical presentations, treatment patterns, and genomic landscape of SCUP.
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