Mayo Clinic Tapestry Study: A Large-Scale Decentralized Whole Exome Sequencing Study for Clinical Practice, Research Discovery, and Genomic Education.

Objective: To execute a large-scale, decentralized, clinical-grade whole exome sequencing study, coined Tapestry, for clinical practice, research discovery, and genomic education.

Patients And Methods: Between July 1, 2020, and May 31, 2024, we invited 1,287,608 adult Mayo Clinic patients to participate in Tapestry. Of those contacted, 114,673 patients were consented and 98,222 (65.

Diagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases.

Background: Though next-generation sequencing (NGS) tests like exome sequencing (ES), genome sequencing (GS), and panels derived from exome and genome data (EGBP) are effective for rare diseases, the ideal diagnostic approach is debated. Limited research has explored reanalyzing raw ES and GS data post-negative EGBP results for diagnostics.

Results: We analyzed complete ES/GS raw sequencing data from Mayo Clinic's Program for Rare and Undiagnosed Diseases (PRaUD) patients to assess whether supplementary findings could augment diagnostic yield.

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants.

Importance: Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed.

Objective: To quantify the risk of development of PDAC and extra-PDAC among first-degree relatives of PDAC probands who carry a PGV in 1 of 9 cancer syndrome-associated genes-ATM, BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, and CDKN2A.

Genomics Integration Into Nephrology Practice.

Rationale & Objective: The etiology of kidney disease remains unknown in many individuals with chronic kidney disease (CKD). We created the Mayo Clinic Nephrology Genomics Clinic to improve our ability to integrate genomic and clinical data to identify the etiology of unexplained CKD.

Study Design: Retrospective study.

Impact of integrated translational research on clinical exome sequencing.

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.

Safety and efficacy of (+)-epicatechin in subjects with Friedreich's ataxia: A phase II, open-label, prospective study.

Background: (+)-Epicatechin (EPI) induces mitochondrial biogenesis and antioxidant metabolism in muscle fibers and neurons. We aimed to evaluate safety and efficacy of (+)-EPI in pediatric subjects with Friedreich's ataxia (FRDA).

Methods: This was a phase II, open-label, baseline-controlled single-center trial including 10 participants ages 10 to 22 with confirmed FA diagnosis.

Three rare disease diagnoses in one patient through exome sequencing.

Diagnostic exome sequencing yields a single genetic diagnosis in ∼30% of cases, and according to recent studies the prevalence of identifying two genetic conditions in a single individual range between 4.6% and 7%. We present a patient diagnosed with three different rare conditions, each explained by a pathogenic variant in a different gene.

Targeted gene approach with biochemical assay confirms ABCD1 mutation of X-linked adrenoleukodystrophy in a 62-year-old man with gait imbalance.

X-linked adrenoleukodystrophy is a peroxisomal disorder caused by a mutation in ABCD1 gene. The three main phenotypes of X-linked adrenoleukodystrophy include cerebral adrenoleukodystrophy, adrenomyeloneuropathy, and isolated primary adrenal insufficiency. More than 750 non-recurrent mutations exist throughout the coding region of the ABCD1 gene.

Phenotypic Variability of c.436delC DCAF17 Gene Mutation in Woodhouse-Sakati Syndrome.

BACKGROUND Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive genetic condition that was first described in 1983. Since its original description, approximately 50 cases have been reported with various clinical signs and symptoms. Characteristics include progressive neurologic deterioration with extrapyramidal involvement and polyendocrinopathy most notable for hypogonadism starting in early adolescence.

Increasing genetic counseling referral rates through bundled interventions after ovarian cancer diagnosis.

Objective: To increase genetic counseling referrals for patients with newly diagnosed epithelial ovarian cancer (EOC).

Methods: A practice-gap analysis was performed after measuring baseline genetic counseling referral rates to identify barriers to referral from the multidisciplinary single institution EOC care group. A Genetics Referral Toolkit consisting of a referral template, a genetic risk checklist, family history worksheet and provider and patient awareness was developed to address identified gaps with the goal of increasing referral rates.

A Novel Kleefstra Syndrome-associated Variant That Affects the Conserved TPL Motif within the Ankyrin Repeat of EHMT1 Leads to Abnormal Protein Folding.

Kleefstra syndrome (KS) (Mendelian Inheritance in Man (MIM) no. 610253), also known as 9q34 deletion syndrome, is an autosomal dominant disorder caused by haploinsufficiency of euchromatic histone methyltransferase-1 (). The clinical phenotype of KS includes moderate to severe intellectual disability with absent speech, hypotonia, brachycephaly, congenital heart defects, and dysmorphic facial features with hypertelorism, synophrys, macroglossia, protruding tongue, and prognathism.

The Genetic Counselor's Role in Managing Ethical Dilemmas Arising in the Laboratory Setting.

Ethical dilemmas are encountered commonly in the setting of the clinical genetic testing laboratory due to the complexity of genetic testing and the number of relevant stakeholders involved in the genetic testing process. Based on their clinical training and role within the laboratory, genetic counselors are uniquely equipped to identify and facilitate management of ethical dilemmas. This paper reviews the historical context of ethical theory and its application to the field of genetic counseling.