A5081123549- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- Congenital heart defects research
- Lysosomal Storage Disorders Research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Epilepsy research and treatment
- Endoplasmic Reticulum Stress and Disease
- Cardiomyopathy and Myosin Studies
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Autophagy in Disease and Therapy
Lucile Packard Children's Hospital
2020-2024
Stanford University
2017-2024
United States Food and Drug Administration
2023
University of California System
2022
Stanford Medicine
2017-2021
Duke University
2021
Neurological Surgery
2020
Palo Alto University
2019
Institute of Neurological Sciences
2018
Abstract Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for and analysis has been a barrier to its use in acutely ill patients. In present study, we develop an approach ultra-rapid nanopore WGS combines optimized sample preparation protocol, distributing over 48 flow cells, near real-time base calling alignment, accelerated variant fast filtration efficient manual review. Application two example clinical cases identified candidate <8...
The Mediator is an evolutionarily conserved, multi-subunit complex that regulates multiple steps of transcription. activity regulated by the reversible association a four-subunit module comprising CDK8 or CDK19 kinases, together with cyclin C, MED12 MED12L, and MED13 MED13L. Mutations in MED12, MED13, MED13L were previously identified syndromic developmental disorders overlapping phenotypes. Here, we report mutations (located at 13q12.13) cause phenotypically related disorder. Using...
Voltage-gated calcium (CaV) channels form three subfamilies (CaV1-3). The CaV1 and CaV2 are heteromeric, consisting of an α1 pore-forming subunit, associated with auxiliary CaVβ α2δ subunits. subunits encoded in mammals by four genes, CACNA2D1-4. They play important roles trafficking function the CaV channel complexes. Here we report biallelic variants CACNA2D1, encoding α2δ-1 protein, two unrelated individuals showing a developmental epileptic encephalopathy. Patient 1 has homozygous...
PurposePathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features described for 11 patients (likely) pathogenic sequence variants. This study aims to further delineate the spectrum of SETD1B-related syndrome based on characterizing an expanded patient cohort.MethodsWe perform in-depth characterization cohort 36 unpublished individuals variants, describing their...
Abstract Background We refine the clinical spectrum of FOXG1 syndrome and expand genotype–phenotype correlations through evaluation 122 individuals enrolled in an international patient registry. Methods The online registry allows for remote collection caregiver-reported outcomes. Inclusion required documentation a (likely) pathogenic variant . Caregivers were administered questionnaire to evaluate severity core features syndrome. Genotype–phenotype determined using nonparametric analyses....
Abstract We report three unrelated probands, two male and one female, diagnosed with Aicardi‐Goutières syndrome (AGS) after screening positive on California newborn (CA NBS) for X‐linked adrenoleukodystrophy (X‐ALD) due to elevated C26:0 lysophosphatidylcholine (C26:0‐LPC). Follow‐up evaluation was notable C26:0, C26:1, C26:0/C22:0 ratio, normal red blood cell plasmalogens levels in all probands. Diagnoses were confirmed by molecular sequencing prior 12 months of age clinical inconsistent...
Due to newborn screening for X-linked adrenoleukodystrophy (ALD), and the use of exome sequencing in clinical practice, detection variants unknown significance (VUS) ABCD1 gene is increasing. In these cases, functional tests fibroblasts may help classify a variant as (likely) benign or pathogenic. We sought establish reference ranges ALD patients control subjects with aim helping determine pathogenicity VUS ABCD1. Fibroblasts from 36 male confirmed ALD, 26 healthy 17 individuals without...
Abstract Background Microcephaly, epilepsy, and diabetes syndrome (MEDS) is a rare syndromic form of monogenic caused by bi-allelic loss function mutations in IER3IP1 . In vitro studies have shown that IER31P leads to apoptosis both neurons pancreatic β-cells. Simultaneous management seizures challenging patients with MEDS. We present the challenges successes use ketogenic diet an infant insulinopenic diabetes. Case presentation Our term female proband presented at 2 months age new onset...
Long read sequencing offers benefits for the detection of structural variation in Mendelian disease. Here, we applied a new technology that generates contiguous long reads via tagmentation and by synthesis to small cohort patients with undiagnosed disease from Undiagnosed Diseases Network. We first compare HG002 benchmark sample Genome In A Bottle using nanopore (R10.4.1, duplex reads, Oxford Nanopore), single molecule real time (Revio SMRT cell, Pacific Biosciences) complete (S4 flowcell,...
Abstract Background FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities. Objectives We describe 2 presenting childhood‐onset nystagmus, seizures carrying pathogenic de novo variants. Weighted gene co‐expression network analysis (WGCNA) was performed to gain insights into the function of brain. Methods Trio‐based whole‐exome sequencing both patients, CoExp web tool used conduct WGCNA . Results Both presented seizures. Previously...
Pseudohypoparathyroidism type 1B (PHP1B) is associated with epigenetic changes on the maternal allele of imprinted GNAS gene that inhibit expression alpha subunit Gs (Gsα), thereby leading to parathyroid hormone resistance in renal proximal tubule cells where Gs from paternal normally silent. Although all patients PHP1B show loss methylation for exon A/B differentially methylated region (DMR), some autosomal dominant (AD-PHP1B) and most sporadic have additional defects affect DMRs...
Infantile spasms (IS) is a neurologic disorder of childhood where time to treatment may affect long-term outcomes. Due the clinical complexity IS, care can be delayed.To determine if use electronic medical record templates (EMRTs) improved quality in patients treated for IS.Records newly diagnosed with IS were retrospectively reviewed both before and after creation an EMRT workup IS. Quality measures included delays plan, medication administration, obtaining neurodiagnostic studies...