A5009062209- Trace Elements in Health
- RNA regulation and disease
- Iron Metabolism and Disorders
- Metabolism and Genetic Disorders
- Heavy Metal Exposure and Toxicity
- Viral Infections and Immunology Research
- Neurological diseases and metabolism
- Infectious Encephalopathies and Encephalitis
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Drug Transport and Resistance Mechanisms
- Genomic variations and chromosomal abnormalities
- Prion Diseases and Protein Misfolding
- Aluminum toxicity and tolerance in plants and animals
- Congenital limb and hand anomalies
- Porphyrin Metabolism and Disorders
- Microbial metabolism and enzyme function
- Virus-based gene therapy research
- Mosquito-borne diseases and control
- Mitochondrial Function and Pathology
- Neonatal and fetal brain pathology
- Fetal and Pediatric Neurological Disorders
- Folate and B Vitamins Research
- Herpesvirus Infections and Treatments
- Blood disorders and treatments
National Institutes of Health
2013-2025
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2015-2025
Nationwide Children's Hospital
1993-2025
The Ohio State University
2020-2025
Columbia University
2025
Gene Therapy Laboratory
2021
Office of Extramural Research
2020
Weatherford College
2016
Molina Center for Energy and the Environment
2012
National Institute on Population Medical Genetics
2010
Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse mutations in copper-transport gene, ATP7A. Early treatment with copper injections may prevent death and illness, but presymptomatic detection hindered the inadequate sensitivity specificity diagnostic tests. Exploiting deficiency enzyme, dopamine-β-hydroxylase, we prospectively evaluated usefulness plasma neurochemical levels, assessed clinical effect early detection, investigated molecular bases for outcomes.
Menkes disease is a neurodegenerative disorder of copper metabolism. Because the enzyme dopamine-beta-hydroxylase requires to catalyze conversion dopamine norepinephrine, we reasoned that patients with would have neurochemical pattern similar seen in congenital absence dopamine-beta-hydroxylase, i.e., high levels dopamine, metabolite dihydroxyphenylacetic acid (DOPAC), and catecholamine precursor dihydroxyphenylalanine (DOPA), low norepinephrine its neuronal dihydroxyphenylglycol (DHPG). We...
Menkes disease is a lethal infantile neurodegenerative disorder of copper metabolism caused by mutations in P-type ATPase, ATP7A. Currently available treatment (daily subcutaneous injections) not entirely effective the majority affected individuals. The mottled-brindled (mo-br) mouse recapitulates phenotype, including abnormal transport to brain owing mutation murine homolog, Atp7a, and dies 14 days age. We documented that mo-br mice on C57BL/6 background were rescued peripheral...
The high-affinity copper transporter CTR1 is encoded by (SLC31A1), a gene locus for which no detailed genotype-phenotype correlations have previously been reported. We describe identical twin male infants homozygous novel missense variant NM_001859.4:c.284 G > A (p.Arg95His) in with distinctive autosomal recessive syndrome of infantile seizures and neurodegeneration, consistent profound central nervous system deficiency. used clinical, biochemical molecular methods to delineate the first...
Abstract The choroid plexuses (CP) are highly vascularized structures that project into the ventricles of vertebrate brain. polarized epithelia CP produce cerebrospinal fluid by transporting water and ions from blood normally secrete a large number proteins. We assessed feasibility selective transduction with recombinant adeno-associated virus (rAAV) gene therapy vectors for treatment lysosomal storage disease (LSD), broad category neurometabolic illness associated significant burdens to...
Abstract Progressive osseous heteroplasia (POH) is a rare autosomal-dominant hereditary bone disorder caused by inactivating pathogenic variants in GNAS1. POH characterized progressive cutaneous ossification and heterotopic skeletal muscles subdermal connective tissues. Understanding of the natural history phenotypic heterogeneity illness incomplete. We report 2 affected male subjects with milder than usual clinical course, highlight their presentations molecular correlates, propose sodium...
Nephropathic cystinosis causes renal failure in most patients at approximately 10 years of age. This can be prevented or retarded by cystine-depleting therapy with oral cysteamine. Many who do not receive adequate cysteamine undergo transplantation, but the accumulation cystine continues other organs, resulting various clinical abnormalities. We report age-related swallowing dysfunction nephropathic cystinosis.We studied 43 (24 had received a transplant and 19 not), 3 to 31 Oral motor...
ATP7A is a P-type ATPase that regulates cellular copper homeostasis by activity at the trans-Golgi network (TGN) and plasma membrane (PM), with location normally governed intracellular concentration. Defects in lead to Menkes disease or its milder variant, occipital horn syndrome newly discovered condition, ATP7A-related distal motor neuropathy (DMN), for which precise pathophysiology has been obscure. We investigated two mutations (T994I, P1386S) previously associated abnormal trafficking....
Previous estimates of the prevalence Menkes disease, a lethal X-linked recessive disorder copper metabolism, were based on confirmed clinical cases ascertained from specific populations and varied 1 in 40,000 to 354,507. With newly available population-based allelic frequencies DNA sequence variants, expected birth disease other ATP7A-related phenotypes can be reconsidered using Hardy-Weinberg theoretical principles. We reviewed canonical ATP7A transcript current version gnomAD (v2.1.1)...
Abstract To correlate genotype with response to early copper histidine therapy in Menkes disease, an X‐linked disorder of transport, we performed mutational analysis 2 related males who began treatment at the age 10 days and prenatally 32 weeks' gestation, respectively. A G T transversion —1 exonic position a splice donor site was identified, predicting glutamine substitution codon 724 copper‐transporting ATPase gene. The Q724H mutation disrupts proper splicing generates five mutant...
Minoxidil is a potent peripheral vasodilating agent used in the treatment of severe hypertension refractory to more conventional therapy. Its use pregnant women and its effect on pregnancy outcome have not previously received attention medical literature. Hypertrichosis well-known side minoxidil.1 It occurs nearly all patients treated for longer than 4 weeks reversible after discontinuation drug.2 We recently observed hypertrichosis multiple congenital anomalies an infant whose mother was...