Publications by authors named "Korf B"
Article Synopsis
- Long-read genome sequencing (lrGS) offers more accurate and comprehensive variant detection for rare diseases compared to short-read genome sequencing (srGS), though its exact impact on diagnostic yield remains unclear.
- In a study involving 96 individuals suspected of having genetic rare diseases, lrGS identified new or potentially relevant genetic variants in 16.7% of participants, with 9.4% possessing pathogenic or likely pathogenic variants.
- While lrGS provided additional insights beyond what was captured by srGS, particularly with structural variations, the study suggests that growing lrGS datasets will further enhance diagnostic capabilities in the future.
Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015-2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States.
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- Researchers identified bi-allelic disruptive variants as the cause of autosomal recessive intellectual developmental disorder type 65, while dominant variants are harder to link to specific traits due to their presence in unaffected individuals.
- The study involved a retrospective analysis of 21 individuals with likely pathogenic variants, focusing on clinical information and molecular data from their families.
- Key findings revealed that those with dominant disruptive variants exhibited more developmental and behavioral problems, while individuals with dominant missense variants had a higher occurrence of renal and skin anomalies, enhancing the understanding of the related neurodevelopmental disorder.
Purpose: We compared the rate of errors in genome sequencing (GS) result disclosures by genetic counselors (GC) and trained non-genetics healthcare professionals (NGHPs) in SouthSeq, a randomized trial utilizing GS in critically ill infants.
Methods: Over 400 recorded GS result disclosures were analyzed for major and minor errors. We used Fisher's exact test to compare error rates between GCs and NGHPs and performed a qualitative content analysis to characterize error themes.
Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs). Currently the only approved therapeutic for NF1 is selumetinib, a mitogen -activated protein kinase (MEK) inhibitor.
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- Long-read genome sequencing (lrGS) outperforms short-read genome sequencing (srGS) in detecting genetic variants associated with rare diseases.
- In a study of 96 probands who tested negative with srGS, lrGS identified new disease-relevant variants in 16.7% of cases, with 8.33% containing pathogenic or likely pathogenic variants.
- lrGS revealed unique variants not detectable by srGS, highlighting that while reanalyzing previous data can improve diagnostic yield, lrGS provides significant additional insights into rare genetic conditions.
Article Synopsis
- * Gene-targeted therapies show potential to address these limitations, but challenges in preclinical and clinical testing, as well as delivery methods, need to be resolved first.
- * Developing better preclinical models, validated assays to measure specific protein activities, and educating patients and clinicians about the risks and benefits of these therapies is crucial for future advancements.
Article Synopsis
- This study investigates patient and parent experiences after participating in an Undiagnosed Diseases Program (UDP) at UAB, using in-depth interviews to gain insights.
- Participants appreciated the opportunity to be seen by the UDP, but their perspectives on the experience varied depending on whether they received a diagnosis.
- The findings highlight positive aspects of the program while revealing unmet needs in communication and follow-up, suggesting areas for improvement that could benefit similar clinics.
Article Synopsis
- - Parents of newborns in the NICU found genome sequencing (GS) valuable for decision-making about future care and resolving diagnostic uncertainties.
- - Most parents accepted the timing of receiving GS results, though they noted the NICU environment could be overwhelming during the process.
- - Parents indicated that GS did not negatively affect their bonding with their infants and had mixed feelings about guilt related to the results.
As the uptake of population screening expands, assessment of medical and psychosocial outcomes is needed. Through the Alabama Genomic Health Initiative (AGHI), a state-funded genomic research program, individuals received screening for pathogenic or likely pathogenic variants in 59 actionable genes via genotyping. Of the 3874 eligible participants that received screening results, 858 (22%) responded to an outcomes survey.
View Article and Find Full Text PDFBackground: Patients with persistent fevers of undetermined etiology often undergo extensive evaluation without a diagnosis. Autoinflammatory syndromes may not always be considered in the differential, as these are rare entities, there are no consensus clinical criteria and genetic testing can only capture a few of these diseases. We aimed to describe the experience and value of an undiagnosed diseases program in the evaluation and management of patients who present with persistent fevers.
View Article and Find Full Text PDFBackground: Prospective data on maintenance therapy with bevacizumab for persons with NF2-related schwannomatosis (NF2-SWN) is lacking. In this prospective multicenter phase II study, we evaluated the efficacy, safety, and tolerability of bevacizumab for maintenance therapy in children and adults with NF2-SWN and hearing loss due to vestibular schwannomas (VS).
Methods: Following induction therapy, participants received bevacizumab 5 mg/kg every 3 weeks for 18 months.
Content: This study examines the potential utility of genetic testing as a supplement to family health history to screen for increased risk of inherited disease. Medical conditions are often misreported or misunderstood, especially those related to different forms of cardiac disease (arrhythmias vs. structural heart disease vs.
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- The study aims to assess the risk of common diseases by considering clinical, monogenic, and polygenic factors, which may be reflected in an individual's family history.
- The eMERGE network is enrolling 25,000 individuals in a prospective study to create and return a comprehensive risk assessment report (GIRA) that includes various genetic risk factors and care recommendations.
- The GIRA report provides actionable guidelines for health care based on genetic data, highlighting the importance of integrating genetic risk assessment into routine health care practices.
Article Synopsis
- The rise of exome and genome sequencing has led to unexpected genetic findings, particularly in pediatric patients, creating challenges for labs and healthcare providers regarding whether to disclose these incidental findings.
- A study involving 21 pediatric patients identified 23 non-ACMG-recommended incidental findings, revealing variability in how different research sites handle the return of these results.
- Although sharing incidental findings can provide insights and benefits to patients, it also poses risks and burdens for healthcare providers, highlighting the need for established guidelines across labs.
Mosaicism in Tumor Suppressor Gene Syndromes: Prevalence, Diagnostic Strategies, and Transmission Risk.
Annu Rev Genomics Hum Genet
August 2022
A mosaic state arises when pathogenic variants are acquired in certain cell lineages during postzygotic development, and mosaic individuals may present with a generalized or localized phenotype. Here, we review the current state of knowledge regarding mosaicism for eight common tumor suppressor genes-, , , , , , , and -and their related genetic syndromes/entities. We compare and discuss approaches for comprehensive diagnostic genetic testing, the spectrum of variant allele frequency, and disease severity.
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