Jorge L. Granadillo
A5062707328- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Protein Tyrosine Phosphatases
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Pediatric Hepatobiliary Diseases and Treatments
- Renal and related cancers
- Genetic Syndromes and Imprinting
- CRISPR and Genetic Engineering
- Drug Transport and Resistance Mechanisms
- Pancreatic function and diabetes
- Chromatin Remodeling and Cancer
- Connective tissue disorders research
- Williams Syndrome Research
- Autism Spectrum Disorder Research
- Cancer-related gene regulation
- Congenital Ear and Nasal Anomalies
- Calcium signaling and nucleotide metabolism
- Metalloenzymes and iron-sulfur proteins
Washington University in St. Louis
2018-2024
St. Louis Children's Hospital
2020-2021
Mallinckrodt (United States)
2020
Universidad Nacional de Colombia
2014
PurposeWe describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across EpiSign diagnostic laboratory network and assessment results impact first subjects tested.MethodsWe outline logistics data flow between an integrated diagnostics laboratories Europe, United States, Canada. We validation using 211 specimens assess test performance yield 207 tested involving two patient subgroups: targeted cohort (subjects with previous ambiguous/inconclusive genetic...
The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only to contain amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized variable combinations developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels PPT-reporters studies...
Abstract Mutations in the orphan transporter MFSD7c (also known as Flvcr2 ), are linked to Fowler syndrome. Here, we used Mfsd7c knockout ( –/– ) mice and cell-based assays reveal that is a choline at blood–brain barrier (BBB). We performed comprehensive metabolomics analysis detected differential changes of metabolites brains livers embryos. Particularly, found choline-related were altered but not Thus, hypothesized regulates level brain. Indeed, expression human cells significantly...
Disease-causing variants in synaptic function genes are a common cause of neurodevelopmental disorders and epilepsy. Here, we describe 14 individuals with de novo disruptive BSN , which encodes the presynaptic protein Bassoon. To expand phenotypic spectrum, identified 15 additional protein-truncating (PTVs) from large biobanks. Clinical features were standardized using Human Phenotype Ontology (HPO) across all 29 individuals, revealed clinical characteristics including epilepsy (13/29 45%),...
SMAD2 is a downstream effector in the TGF-β signaling pathway, which important for pattern formation and tissue differentiation. Pathogenic variants have been reported association with arterial aneurysms dissections large cohorts of subjects complex congenital heart disease (CHD). We used whole exome sequencing (WES) to investigate molecular cause CHD other anomalies three probands an aneurysm additional patient. Patients 1 2 presented CHD, developmental delay, seizures, dysmorphic features,...
Background Rare variants in hundreds of genes have been implicated developmental delay (DD), intellectual disability (ID) and neurobehavioural phenotypes. TNRC6B encodes a protein important for RNA silencing. Heterozygous truncating reported three patients from large cohorts with autism, but no full phenotypic characterisation was described. Methods Clinical molecular performed on 17 variants. data were obtained by retrospective chart review, parent interviews, direct patient interaction...
PurposeThis study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in NR4A2 gene.MethodsVariants were identified origins confirmed through trio exome sequencing all but one patient. Targeted RNA was performed for variant to confirm its splicing effect. Independent discoveries shared GeneMatcher.ResultsMissense loss-of-function from eight families. One patient carried a larger deletion including adjacent genes. The cases presented developmental...
Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with display macrocephaly/megalencephaly, developmental delay, intellectual disability, seizures. A few dozen are reported literature. Here, we report cohort of 28 that represent nine pathogenic variants. We conducted detailed natural history study found pathophysiological deficits among addition to common...
Abstract The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism, behavioral disruptions, aggression, obesity epilepsy. While is expressed throughout the brain, how it function distinct regions has not been assessed. Some features of Neurodevelopmental Syndrome suggest disruption hypothalamic function, such...
Abstract Chromodomain helicase DNA‐binding protein 7 ( CHD7 ) pathogenic variants are identified in more than 90% of infants and children with CHARGE C oloboma the iris, retina, and/or optic disk; congenital H eart defects, choanal A tresia, R etardation growth development, G enital hypoplasia, characteristic outer inner E ar anomalies deafness) syndrome. Approximately, 10% cases have no known genetic cause identified. We report a male child clinical features syndrome nondiagnostic testing...
13q12.3 microdeletion syndrome is a rare cause of syndromic intellectual disability. Identification and genetic characterization patients with continues to expand the phenotypic spectrum associated it. Previous studies identified four genes within approximately 300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 HMGB1. To date, no carrying sequence-level variant or single gene deletion in HMGB1 have been described. Here we report six loss-of-function variants...
GATA zinc finger domain containing 2A (GATAD2A) is a subunit of the nucleosome remodeling and deacetylase (NuRD) complex. NuRD known to regulate gene expression during neural development other processes. The complex modulates chromatin status through histone deacetylation ATP-dependent activities. Several neurodevelopmental disorders (NDDs) have been previously linked variants in components NuRD's subcomplex (NuRDopathies). We identified five individuals with features an NDD that possessed...
Protein-tyrosine phosphatases (PTPs) are pleomorphic regulators of eukaryotic cellular responses to extracellular signals that function by modulating the phosphotyrosine specific proteins. A handful PTPs have been implicated in germline and somatic human disease. Using exome sequencing, we identified missense truncating variants PTPN4 six unrelated individuals with varying degrees intellectual disability or developmental delay. The occurred de novo all five subjects whom segregation analysis...
We report a patient harboring de novo m.5540G>A mutation affecting the MT-TW gene coding for mitochondrial tryptophan-transfer RNA. This presented with atonic–myoclonic epilepsy, bilateral sensorineural hearing loss, ataxia, motor regression, ptosis, and pigmentary retinopathy. Our proband had an earlier onset more severe phenotype than first reported same mutation. discuss her clinical presentation compare it only previously published case.
ABSTRACT Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore Syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with display macrocephaly/megalencephaly, developmental delay, intellectual disability, seizures. A few dozen are reported literature. Here, we report cohort of 28 that represent 9 new pathogenic variants, including p.R1480_C1483del Δ(R1480-C1483). We conducted detailed natural history study on these patients...
Jarasvaraparn, Chaowapong∗; He, Mai†; Granadillo, Jorge L.‡; Kulkarni, Sakil∗; Stoll, Janis∗; Liss, Kim∗Author Information