Paul J. Lockhart

Mahi-mahi accurately genotypes repeat expansions from nanopore sequencing data, matching orthogonal methods and identifying pathogenic alleles.

This study uses deep sequencing to identify genetic variants in focal cortical dysplasias, finding pathogenic variants in 71% of cases and highlighting the importance of somatic variants in FCDIIb.

This paper develops a calibrated electrophysiological framework to classify CACNA1G missense variants, identifying two variants as likely pathogenic and others as benign.

The paper identifies a chimeric CLMN::SYNE3 RNA transcript from a 14q32.13 duplication as the cause of SCA30, a form of cerebellar ataxia, through RNA-Seq and functional studies.

This study identifies conserved microglial miRNAs across species and their preserved function in demyelination and remyelination.

The paper examines how modifier variants affect clinical outcomes in individuals with primary disease variants, showing context-dependent phenotypic associations and synergistic interactions.

The paper develops a framework to study variable expressivity in genetic disorders using 16p12.1 deletion models, showing how genetic background and secondary variants influence gene expression and phenotypes.

The paper develops an automated tool for reanalyzing genomic data in rare disease cohorts, showing improved diagnostic yields through iterative reanalysis.

The paper uses long-read sequencing data to analyze STR variability across 2,645 individuals, identifying disease-associated STR loci with elevated allelic variability and introducing the PLVI metric.

This study identifies the complete sequences of pathogenic and non-pathogenic FGF14 repeat expansions in patients with cerebellar ataxia, revealing a lower pathogenic threshold and providing mechanistic insights into disease causation.

Mostly de novo variants in an 18 bp constrained region of U4 snRNA gene RNU4-2 cause a syndromic neurodevelopmental disorder, estimated to explain 0.41% of cases.

This study compares short-read and long-read sequencing for diagnosing cerebellar ataxia, finding both effective but with different strengths in repeat expansion detection.

This study creates a mouse model of mosaic Slc35a2 knockout to study its impact on cortical development and epilepsy-related traits.

The paper examines how assortative mating and parental genetic relatedness influence the pathogenicity of variably expressive variants in neurodevelopmental disorders.

This study identifies a novel intronic GAA repeat expansion in FGF14 as a cause of autosomal dominant adult-onset ataxia, with (GAA)>335 being fully penetrant and (GAA)>250 likely pathogenic.

This study shows that DCC and NTN1 regulate astroglial development and interhemispheric fissure remodeling, essential for corpus callosum and hippocampal commissure formation.

The paper identifies four psychological endophenotypes of the Broader Autism Phenotype using phenotyping in large multiplex families and shows high sensitivity and specificity for BAP classification.

The paper evaluates the prevalence of RFC1 and DAB1 repeat expansions in an undiagnosed ataxia cohort, finding biallelic RFC1 expansions in 2.7% of patients.

This study uses whole genome sequencing to rapidly diagnose SCA36 in a family, demonstrating the feasibility and cost-effectiveness of WGS for repeat expansion detection.

This study validates new bioinformatic tools to identify expanded repeats, discovering a novel intronic pentamer expansion in RFC1 causing CANVAS.

This study shows that resecting only the center of cortical tubers in TSC patients eliminates seizures without functional deficits, as the center has higher dysmorphic neuron density.

The paper introduces exSTRa, a method to detect repeat expansions in WES and WGS data, showing superior performance for WES compared to existing methods.

The paper identifies a hypomorphic MMP14 mutation in Winchester syndrome and shows its catalytic activity determines disease severity using in vitro and zebrafish models.