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Open AccessDiagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases
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 appr...
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Article
Semiautomated approach focused on new genomic information results in time and effort-efficient reannotation of negative exome data
Most rare disease patients (75–50%) undergoing genomic sequencing remain unsolved, often due to lack of information about variants identified. Data review over time can leverage novel information regarding dis...
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Open AccessCorrection: Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)
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Open AccessIdentification of skewed X chromosome inactivation using exome and transcriptome sequencing in patients with suspected rare genetic disease
X-chromosome inactivation (XCI) is an epigenetic process that occurs during early development in mammalian females by randomly silencing one of two copies of the X chromosome in each cell. The preferential ina...
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Article
Open AccessBi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlap** phe...
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Open AccessImplementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)
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 und...
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Open AccessExome sequencing can misread high variant allele fraction of somatic variants in UBA1 as hemizygous in VEXAS syndrome: a case report
VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) is a recently described syndrome caused by a somatic missense variant at the methionine-41 (p.(Met41)) position in the ubiquit...
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Interpretation of Dihydrorhodamine-1,2,3 Flow Cytometry in Chronic Granulomatous Disease: an Atypical Exemplar
This is a functional characterization of a novel CYBA variant associated with normal DHR flow cytometry. Chronic granulomatous disease (CGD) is an inborn error of immunity characterized by recurrent bacterial and...
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Article
Open AccessGain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome
Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (...
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Article
Open AccessDesign considerations for workflow management systems use in production genomics research and the clinic
The changing landscape of genomics research and clinical practice has created a need for computational pipelines capable of efficiently orchestrating complex analysis stages while handling large volumes of dat...
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Open AccessClinical and molecular correlates from a predominantly adult cohort of patients with short telomere lengths
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Open AccessHELLO: improved neural network architectures and methodologies for small variant calling
Modern Next Generation- and Third Generation- Sequencing methods such as Illumina and PacBio Circular Consensus Sequencing platforms provide accurate sequencing data. Parallel developments in Deep Learning hav...
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Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome
SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organizat...
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Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics
Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic ...
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Article
Open AccessEpigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, ...
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Open AccessImpairment of the mitochondrial one-carbon metabolism enzyme SHMT2 causes a novel brain and heart developmental syndrome
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Open AccessFunctional validation of TERT and TERC variants of uncertain significance in patients with short telomere syndromes
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Open AccessNovel loss-of-function variants in TRIO are associated with neurodevelopmental disorder: case report
Damaging variants in TRIO have been associated with moderate to severe neurodevelopmental disorders in humans. While recent work has delineated the positional effect of missense variation on the resulting phenoty...
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Open AccessBest practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease
Whole-genome sequencing (WGS) has shown promise in becoming a first-tier diagnostic test for patients with rare genetic disorders; however, standards addressing the definition and deployment practice of a best...
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Successful Treatment of Skewed Lyonization Associated with X-Linked CGD in a Female Presenting with Recalcitrant Crohn’s Disease
