A5091017049- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- Vascular Malformations and Hemangiomas
- Epilepsy research and treatment
- Mitochondrial Function and Pathology
- Cancer Genomics and Diagnostics
- Genetic Syndromes and Imprinting
- Autism Spectrum Disorder Research
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Spinal Dysraphism and Malformations
- Genetic factors in colorectal cancer
- Magnesium in Health and Disease
- Child Development and Digital Technology
- Assisted Reproductive Technology and Twin Pregnancy
- Carbohydrate Chemistry and Synthesis
- Skin and Cellular Biology Research
- Plant Micronutrient Interactions and Effects
- ATP Synthase and ATPases Research
- Connective tissue disorders research
- CRISPR and Genetic Engineering
- Congenital heart defects research
- Genetic and Kidney Cyst Diseases
Greenwood Genetic Center
2021-2024
Emory University
2016-2022
GABAA receptors are ligand-gated anion channels that important regulators of neuronal inhibition. Mutations in several genes encoding receptor subunits have been identified patients with various types epilepsy, ranging from mild febrile seizures to severe epileptic encephalopathy. Using whole-genome sequencing, we a novel de novo missense variant GABRA5 (c.880G > C, p.V294L) patient early-onset epilepsy and developmental delay. Targeted resequencing 279 additional 19 rare variants nine...
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%),...
Summary Previous reports have identified SLC 6A1 variants in patients with generalized epilepsies, such as myoclonic‐atonic epilepsy and childhood absence epilepsy. However, to date, none of the has been functionally tested for an effect on GAT ‐1 transporter activity. The purpose this study was determine incidence 460 unselected evaluate impact γ‐aminobutyric acid (GABA)transport. Targeted resequencing used screen . Five missense variants, one in‐frame deletion, nonsense variant, intronic...
Abstract The vacuolar H+-ATPase is an enzymatic complex that functions in ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants ATP6V0C, encoding c-subunit bound integral domain H+-ATPase, 27 patients with neurodevelopmental abnormalities or without epilepsy. Corpus callosum hypoplasia cardiac were also present...
Abstract Background Rett syndrome (RTT) is a rare neurodevelopmental disorder associated with pathogenic MECP2 variants. Because the gene subject to X‐chromosome inactivation (XCI), factors including genotypic variation, tissue differences in XCI, and skewing of XCI all likely contribute clinical severity individuals RTT. Methods We analyzed patterns from blood samples 320 their mothers. It includes RTT ( n = 287) other syndromes sharing overlapping phenotypes (such as CDKL5 Deficiency...
CACNA2D2 encodes an auxiliary subunit of the voltage-dependent calcium channel. To date, there have only been two reports individuals with early-infantile epileptic encephalopathy due to mutations. In both reports, patients were homozygous for identified variants. Here, we report a patient and cerebellar atrophy who was found novel variants in gene: c.782C>T (p.Pro261Leu) c.3137T>C (p.Leu1046Pro), by whole-exome sequencing. The shown be inherited trans unaffected parents confirmed...
We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,caused by
Abstract Mutations in the voltage‐gated sodium channel gene SCN8A cause a broad range of human diseases, including epilepsy, intellectual disability, and ataxia. Here we describe three mouse lines on C57BL/6J background with novel, overlapping mutations Scn8a DIIS4 voltage sensor: an in‐frame 9 bp deletion ( Δ9 ), 3 insertion ∇3 ) 35 that results frameshift generation null allele Δ35 ). Δ9/+ ∇3/+ heterozygous mutants display subtle motor deficits, reduced acoustic startle response, are...
Chromosomal aneuploidies, microduplications and microdeletions are the most common confirmed genetic causes of spina bifida. Microduplications Xq27 containing SOX3 gene have been reported in 11 cases, confirming existence an X-chromosomal locus for A three generation kindred here with a duplication has identified one 17 kindreds recurrences 29 years South Carolina Neural Tube Defect Prevention Program. Other during this time period included siblings APAF1 mutation, CASP9 microdeletion 13q,...
Abstract Background We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in degron of AFF3. Mouse knock-ins overexpression zebrafish provided evidence for a dominant-negative mode action, wherein increased level AFF3 resulted pathological effects. Methods Evolutionary constraints suggest that other modes-of-inheritance could be at play. challenged this...
ABSTRACT Background Heterozygous variants in Transient receptor potential melastatin type 7 (TRPM7), encoding an essential and ubiquitously expressed cation channel, may cause hypomagnesemia, but current evidence is insufficient to draw definite conclusions it unclear whether any other phenotypes can occur. Methods Individuals with unexplained hypomagnesemia underwent whole-exome sequencing which identified TRPM7 variants. Pathogenicity of the was assessed by combining phenotypic, functional...
Numerous SCN8A mutations have been identified, of which, the majority are de novo missense variants. Most result in epileptic encephalopathy; however, some associated with less severe phenotypes. Mouse models generated by knock-in human exhibit seizures and a range behavioral abnormalities. To date, there only few Scn8a mouse in-frame deletions or insertions, notably, none these lines increased seizure susceptibility. In current study, we report generation characterization two (ΔIRL/+...