Germline pathogenic variants (PVs) in CBL are found in 15 % of juvenile myelomonocytic leukemia (JMML) cases. Here we report three siblings with CBL(NM_005188):c.1111T>C variation presenting a heterogenous JMML clinic and outcome.
View Article and Find Full Text PDFBackground: Intellectual developmental disorder with autism and speech delay (IDDAS) is a rare and complex neurological disorder characterized by the presence of both intellectual and speech impairment and features of autism spectrum disorder (ASD). The prevalence of IDDAS is unknown but genetically, it is caused by heterozygous variants in the gene.
Methods: A 7-year-old female with autistic features and delayed speech development was presented with unaffected parents.
() is a tumor suppressor gene involved in DNA repair and cell cycle regulation. Pathogenic or likely pathogenic (P/LP) variants in are associated with increased cancer risk. Conversely, recent large cohort studies have identified certain variants that, despite being classified as P/LP by in silico analysis, are considered low risk.
View Article and Find Full Text PDFBackground: The phenotypic spectrum of muscle disease ranges widely from elevated creatine kinase (CK) levels in the serum of asymptomatic individuals to progressive muscular dystrophy. Due to overlapping clinical features among muscular dystrophies, the diagnosis of muscle disease is established by molecular genetic tests. Early diagnosis is crucial for the clinical management of symptoms and to mitigate cardiac and musculoskeletal complications.
View Article and Find Full Text PDFSmith-Magenis syndrome is a complex neurobehavioral genetic disorder with a broad phenotypic spectrum. While the etiology of SMS is commonly attributed to one-copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in have also been reported in 5-10% of cases.
View Article and Find Full Text PDFATM gene is implicated in the development of breast cancer in the heterozygous state, and Ataxia-telangiectasia (A-T) in a homozygous or compound heterozygous state. Ataxia-telangiectasia (A-T) is a rare cerebellar ataxia syndrome presenting with progressive neurologic impairment, telangiectasia, and an increased risk of leukemia and lymphoma. Although the role of ATM, separately, in association with A-T and breast cancer is well documented, there is a limited number of studies investigating ATM variants when segregating with both phenotypes in the same family.
View Article and Find Full Text PDFPurpose: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS).
Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected.
BACKGROUND Neurodevelopmental disorders (NDD) are umbrella disorders that encompass global developmental delay (GDD), intellectual disability, autism spectrum disorders, motor developmental disorders, and sleep disorders. Both GDD and autism spectrum disorder are common and yet clinically and genetically heterogeneous disorders. Despite their high prevalence and the advent of sequencing detection methods, the genomic etiology of GDD and autism spectrum disorder in most patients is largely unknown.
View Article and Find Full Text PDFStandard methods of variant assessment in hereditary cancer susceptibility genes are limited by the lack of availability of key supporting evidence. In cancer, information derived from tumors can serve as a useful source in delineating the tumor behavior and the role of germline variants in tumor progression. We have previously demonstrated the value of integrating tumor and germline findings to comprehensively assess germline variants in hereditary cancer syndromes.
View Article and Find Full Text PDFThe presence of variants of uncertain significance (VUS) in DNA mismatch repair (MMR) genes leads to uncertainty in the clinical management of patients being evaluated for Lynch syndrome (LS). Currently, there is no platform to systematically use tumor-derived evidence alongside germline data for the assessment of VUS in relation to LS. We developed INTGRATE (INTegrated INTerpretation of GeRmline And Tumor gEnomes) to leverage information from the tumor genome to inform the potential role of constitutional VUS in MMR genes.
View Article and Find Full Text PDFCaesarean section has risks of bleeding, infection and thromboembolism, and neuroendocrine-metabolic, and inflammatory-immune responses that may worsen outcomes in patients with preeclampsia. There is little research examining perioperative, as opposed to peripartum, outcomes in patients with preeclampsia. We conducted a single-centrecentre retrospective cohort study of perioperative patients with preeclampsia over an eight-month period to determine the rate of perioperative complication.
View Article and Find Full Text PDFConcurrent pathogenic variants (PVs) in cancer predisposition genes have been reported in 0.1-2% of hereditary cancer (HC) patients. Determining concurrent PVs is crucial for the diagnosis, treatment, and risk assessment of unaffected family members.
View Article and Find Full Text PDFBackground And Aim: The impact of chronic hepatitis B virus (HBV) infection and nucleos(t)ide analogue (NUC) treatment on disease severity and clinical outcomes in patients with coronavirus 2019 (COVID-19) is unknown. The objective of this study was to determine whether HBV infection and the use of NUCs impacts mortality in patients with COVID-19.
Materials And Methods: A total of 231 adult patients (77 with COVID-19 and HBV coinfection) with a laboratory-confirmed diagnosis of COVID-19 were enrolled in this retrospective study.
Introduction: Since the beginning of the pandemic, factors associated with mortality in patients with corona virus infection disease 2019 (COVID-19) have been investigated. Comorbidities and increased age have been frequently reported to be associated with mortality. We aimed to evaluate the factors associated with unfavorable outcome of patients with COVID-19 at an early period of the pandemic.
View Article and Find Full Text PDF-mutated breast cancers have specific pathological characteristics. is a tumor suppressor gene that is important in many cancers with different pathways. The relationship between mutation and BAP1 immunohistochemical staining is still unclear.
View Article and Find Full Text PDFBackground: Copy number variations (CNVs) are commonly associated with malignancies, including hereditary breast and ovarian cancers. Next generation sequencing (NGS) provides solutions for CNV detection in a single run. This study aimed to compare the accuracy of CNV detection by NGS analyzing tool against Multiplex Ligation Dependent Probe Amplification (MLPA).
View Article and Find Full Text PDFNext-generation sequencing (NGS) is used increasingly in hereditary cancer patients' (HCP) management. While enabling evaluation of multiple genes simultaneously, the technology brings to light the dilemma of variant interpretation. Here, we aimed to reveal the underlying reasons for the discrepancy in the evidence titles used during variant classification according to ACMG guidelines by two different bioinformatic specialists (BIs) and two different clinical geneticists (CGs).
View Article and Find Full Text PDFBackground/aim: Coronavirus 2019 disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic infectious disease that causes morbidity and mortality. As a result of high mortality rate among the severe COVID-19 patients, the early detection of the disease stage and early effective interventions are very important in reducing mortality. Hence, it is important to differentiate severe and nonsevere cases from each other.
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