يعرض 1 - 6 نتائج من 6 نتيجة بحث عن '"Sarah A. Kroc"', وقت الاستعلام: 0.88s تنقيح النتائج
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    دورية أكاديمية

    المصدر: Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-2 (2024)

    مصطلحات موضوعية: Medicine

    وصف الملف: electronic resource

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    دورية أكاديمية

    المصدر: Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-10 (2023)

    الوصف: Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

    وصف الملف: electronic resource

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    المصدر: Genetics in Medicine. 25:100359

    الوصف: Purpose Exome sequencing often identifies pathogenic genetic variants in patients with undiagnosed diseases. Nevertheless, frequent findings of variants of uncertain significance necessitate additional efforts to establish causality before reaching a conclusive diagnosis. To provide comprehensive genomic testing to patients with undiagnosed disease, we established an Individualized Medicine Clinic, which offered clinical exome testing and included a Translational Omics Program (TOP) that provided variant curation, research activities, or research exome sequencing. Methods From 2012 to 2018, 1101 unselected patients with undiagnosed diseases received exome testing. Outcomes were reviewed to assess impact of the TOP and patient characteristics on diagnostic rates through descriptive and multivariate analyses. Results The overall diagnostic yield was 24.9% (274 of 1101 patients), with 174 (15.8% of 1101) diagnosed on the basis of clinical exome sequencing alone. Four hundred twenty-three patients with nondiagnostic or without access to clinical exome sequencing were evaluated by the TOP, with 100 (9% of 1101) patients receiving a diagnosis, accounting for 36.5% of the diagnostic yield. The identification of a genetic diagnosis was influenced by the age at time of testing and the disease phenotype of the patient. Conclusion Integration of translational research activities into clinical practice of a tertiary medical center can significantly increase the diagnostic yield of patients with undiagnosed disease.

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    المصدر: Gynecologic Oncology. 162:S185-S186

    الوصف: Objectives: Women with epithelial ovarian cancer (EOC) who have a germline mutation, somatic mutation or are found to have homologous recombination deficiency (HRD) have been shown to have an improved survival with use of a PARP inhibitor after completion of first-line chemotherapy. A quality improvement project aimed to develop a pathway for somatic/HRD testing in all patients with EOC. Methods: Standard quality improvement methodology was employed to complete a stakeholder analysis, process mapping, an Ishikawa diagram, a pro/con brainstorming session and a provider survey. Additionally, we benchmarked with another academic institution. Patient education material on genetic testing was developed. Plan-Do-Study-Act (PDSA) cycles were employed throughout the quality improvement process. All newly diagnosed patients with EOC who underwent surgery between January - June 2019 (preimplementation) and June-August 2020 (post-implementation) were identified. Data was abstracted from medical records to determine which patients were referred to genetics and which patients were provided with somatic testing recommendations. Results: Prior to implementation, 42.9% (30/70) patients who completed primary treatment of EOC had somatic testing ordered prior to completing primary adjuvant chemotherapy. Post-implementation, 63% (17/27) of patients had somatic testing recommended. Confining analysis to those patients who returned for a postoperative visit at the surgical institution, 77.8% (14/18) had somatic testing recommended. Germline testing referral and rates (countermeasure) did not change 88.6% (62/70) vs 85.3% (29/34) (pre versus post-implementation). Conclusions: Development of a structured process for somatic/HRD testing after surgery for EOC results improved rates of somatic testing discussion. A stepwise process ensures that these patients still receive the necessary counseling about germline testing prior to undergoing somatic/HRD testing.

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    المصدر: Hum Mol Genet

    الوصف: SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.