Rare germline
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Exome sequencing (ES) is a first-tier diagnostic test for many suspected Mendelian disorders. While it is routine to detect small sequence variants, it is not a standard practice in clinical settings to detect germline copynumber variants (CNVs) from ES data due to several reasons relating to performance. In this work, we comprehensively characterized one of the most sensitive ES-based CNV tools.
11p vibransone 28-03-2024 2 2 Download
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Renal medullary carcinomas (RMCs) are rare kidney cancers that occur in adolescents and young adults of African ancestry. Although RMC is associated with the sickle cell trait and somatic loss of the tumor suppressor, SMARCB1, the ancestral origins of RMC remain unknown. Further, characterization of structural variants (SVs) involving SMARCB1 in RMC remains limited.
13p vibransone 28-03-2024 3 2 Download
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Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent.
14p vibransone 28-03-2024 4 2 Download
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To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workfows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increase efciency. We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline genetic diagnosis for rare disease.
11p vicwell 29-02-2024 4 2 Download
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Damaging alterations in the BRCA1 gene have been extensively described as one of the main causes of hereditary breast and ovarian cancer (HBOC).BRCA1 alterations can lead to impaired homologous recombination repair (HRR) of double-stranded DNA breaks, a process which involves the RING, BRCT and coiled-coil domains of the BRCA1 protein.
13p vischultz 20-10-2023 1 1 Download
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Retinoblastoma (Rb) is a rare cancer that develops from the layer of cells in the retina. A germline mutation in the RB1 gene is a high risk factor for Rb. We performed prenatal genetic diagnosis on two pregnant women who had had a child with hereditary Rb and continued checking their newborns' conditions after giving birth
6p vimulcahy 18-09-2023 6 3 Download
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Surveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire.
9p vinarcissa 21-03-2023 2 1 Download
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Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fuoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice.
8p vielonmusk 21-01-2022 9 0 Download
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Identifying rare germline and somatic variants associated with cancer progression is an important research topic in cancer genomics. Although many approaches are proposed for rare variant association study, they are not fit for cancer sequencing data due to multiple issues, such as overly relying on pre-selection, losing sight of interacting hotspots, etc.
8p vilarryellison 29-10-2021 9 0 Download
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The C:G > T:A substitution at the CpG dinucleotide contexts is the most frequent substitution type in genome evolution. The mutational process is obviously ongoing in the human germline; however, its impact on common and rare genomic polymorphisms has not been comprehensively investigated yet.
11p vijeeni2711 24-07-2021 11 0 Download
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The Birt–Hogg–Dubé (BHD) syndrome is a very rare autosomal dominant form of genodermatosis caused by germline mutations in the folliculin (FLCN) gene, which is mapped to the p11.2 region in chromosome 17.
6p vimaine2711 26-03-2021 15 2 Download
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Characterising genetic diversity through the analysis of massively parallel sequencing (MPS) data offers enormous potential to significantly improve our understanding of the genetic basis for observed phenotypes, including predisposition to and progression of complex human disease.
9p viwyoming2711 16-12-2020 17 0 Download
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In standard high throughput sequencing analysis, genetic variants are not assigned to a homologous chromosome of origin. This process, called haplotype phasing, can reveal information important for understanding the relationship between genetic variants and biological phenotypes.
11p vijisoo2711 27-10-2020 11 1 Download
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Rare, heterozygous germline mutations in the RAD51C gene have been found in breast and ovarian cancer families. In the Finnish population, we have identified two founder mutations in RAD51C that increase the risk of ovarian cancer but not breast cancer in the absence of ovarian cancer. Risk for other cancers has not been studied.
4p vijisoo2711 30-09-2020 5 1 Download
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Most currently known breast cancer predisposition genes play a role in DNA repair by homologous recombination. Recent studies conducted on RAD51 paralogs, involved in the same DNA repair pathway, have identified rare germline mutations conferring breast and/or ovarian cancer predisposition in the RAD51C, RAD51D and XRCC2 genes.
8p vijennie2711 29-09-2020 9 0 Download
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Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands.
11p virose2711 22-09-2020 12 1 Download
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Median overall survival (OS) of patients with melanoma brain metastases (MBM) is usually 6 months or less. There are rare reports of patients with treated MBM who survived for years. These outlier cases represent valuable opportunities to study the somatic and germline factors that may have influenced patient outcome and led to extended survival.
6p vimoscow2711 29-08-2020 8 1 Download
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Melanotic neuroectodermal tumor of infancy (MNTI) is exceptionally rare and occurs predominantly in the head and neck (92.8 % cases). The patient reported here is only the eighth case of MNTI presenting in an extremity, and the first reported in the fibula.
14p vimale2711 25-08-2020 7 2 Download
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Multiple Myeloma is a cancer of plasma cells associated with significantly reduced survival. Long term survivorship from myeloma is very rare and despite advances in its treatment the disease is generally considered incurable.
6p vimanama2711 30-07-2020 13 1 Download
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Familial cases of appendiceal mucinous tumours (AMTs) are extremely rare and the underlying genetic aetiology uncertain. We identified potential predisposing germline genetic variants in a father and daughter with AMTs presenting with pseudomyxoma peritonei (PMP) and correlated these with regions of loss of heterozygosity (LOH) in the tumours.
9p viorochimaru2711 01-06-2020 8 1 Download