Eric A. Pierce

In vitro pathogenicity evaluation of deep intronic variants for recessive genetic retinal diseases

This study evaluates the pathogenicity of deep intronic variants in recessive retinal diseases using a high-throughput splicing assay, finding that 19.4% of variants activate cryptic exons.

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing

This study evaluates the diagnostic yield of short-read and long-read sequencing in rare diseases, finding limited added value from long-read sequencing despite increased variant discovery.

Oxidative DNA Damage Drives Apoptotic Photoreceptor Loss in NMNAT1-Associated Inherited Retinal Degeneration: A Therapeutic Opportunity

This study shows that oxidative DNA damage causes photoreceptor loss in NMNAT1-related retinal degeneration and that NAC treatment reduces damage and preserves vision.

Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases

The paper identifies mitochondrial DNA variants in undiagnosed rare disease families using exome and genome sequencing data, leading to diagnoses in 0.4% of cases.

Systematic empirical evaluation of individual base editing targets: validating therapeutic targets in USH2A and comparison of methods

The paper evaluates base editing efficiency for USH2A mutations using in vitro screening and a mouse model, showing high correction rates and comparing methods.

Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease

The paper detects and classifies copy number variants in exome data from 6,633 families, identifying causal CNVs in 173 families and improving classification standards.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

This study evaluates genome sequencing's diagnostic yield in a cohort of undiagnosed rare disease patients, finding it solves 29.3% of cases with specific variant types not detectable by exome sequencing.

A high throughput splicing assay to investigate the effect of variants of unknown significance on exon inclusion

The paper develops a high throughput splicing assay (HTSA) to assess the impact of variants of unknown significance on exon inclusion, identifying 47 variants that significantly reduce exon recognition.

Expression of NMNAT1 in the Photoreceptors is Sufficient to Prevent NMNAT1-Associated Disease

This study shows that expressing NMNAT1 specifically in photoreceptors prevents retinal degeneration in a mouse model of NMNAT1-associated disease.

The RNA Content of Extracellular Vesicles from PRPF31+/- hiPSC-RPE Show Potential as Biomarkers of Retinal Degeneration

The paper investigates RNA profiles in extracellular vesicles from PRPF31 mutant hi-RPE cells, finding distinct RNA content that may serve as biomarkers for retinal degeneration.

The Importance of Automation in Genetic Diagnosis: Lessons from Analyzing an Inherited Retinal Degeneration Cohort with the Mendelian Analysis Toolkit (MATK)

The paper introduces MATK, an automated variant ranking tool for Mendelian disease diagnosis, showing it identifies most expert solutions and finds additional variants in unsolved cases.

Early onset non-syndromic retinal degeneration due to variants in INPP5E: phenotypic expansion of the ciliary gene previously associated with Joubert syndrome

The paper identifies INPP5E variants in non-syndromic retinal degenerations, expanding the known phenotypic spectrum of this ciliary gene.

Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice.

This study shows that C5 ablation does not prevent sub-RPE deposit formation in Efemp1 mutant mice, suggesting C3, not C5, may be a better therapeutic target for early AMD.

Evaluating Methods for Differential Gene Expression And Alternative Splicing Using Internal Synthetic Controls.

The paper evaluates methods for detecting differential gene expression, differential transcript expression, and alternative splicing using internal synthetic controls in RNA-seq data.

Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations

The paper identifies copy-number variations (CNVs) as a significant contributor to unsolved inherited retinal degeneration (IRD) cases, increasing the genetic diagnostic rate through NGS-based CNV detection.

Exon 13-skipped USH2A protein retains functional integrity in mice, suggesting an exon skipping therapeutic approach to treat USH2A-associated disease.

This study shows that skipping exon 13 of the USH2A gene produces functional Usherin protein in mice, supporting exon-skipping as a therapeutic approach for USH2A-related diseases.

A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families.

The paper combines whole genome sequencing and retinal organoid transcriptome analysis to identify and validate a novel non-coding pathogenic variant in a family with an unresolved genetic diagnosis.

AAV-mediated gene augmentation therapy restores critical functions in mutant iPSC-derived PRPF31+/- cells.

This study shows that AAV-mediated gene augmentation therapy can restore critical functions in PRPF31 mutant iPSC-derived RPE cells, providing proof-of-concept for treating PRPF31-related retinitis pigmentosa.

Characterizing variants of unknown significance inrhodopsin: a functional genomics approach

This study develops a high-throughput cell-based assay to functionally characterize pathogenic variants of unknown significance in rhodopsin, recategorizing 37 variants and validating results across assays.

Contribution of non-coding mutations to RPGRIP1-mediated inherited retinal degeneration.

The paper identifies non-coding mutations as a significant cause of RPGRIP1-mediated inherited retinal degeneration in patients with single coding mutations.

Ift172 conditional knockout mice exhibit rapid retinal degeneration and protein trafficking defects

This study creates a mouse model of IFT172-associated retinal degeneration and shows that IFT172 depletion causes rapid retinal degeneration and protein trafficking defects.

Allele-specific CRISPR/Cas9 genome editing of the single-base P23H mutation for rhodopsin associated dominant retinitis pigmentosa

This study demonstrates allele-specific CRISPR/Cas9 editing of the P23H mutation in Rho-P23H mice, reducing mutant allele expression and delaying photoreceptor degeneration.

Human iPSC-derived RPE and retinal organoids reveal impaired alternative splicing of genes involved in pre-mRNA splicing in PRPF31 autosomal dominant retinitis pigmentosa

The paper generates patient-specific retinal organoids and RPE from RP type 11 patients to show PRPF31 mutations cause retinal-specific splicing defects and structural/functional impairments, which are corrected by in situ gene editing.