A5034442407- Ion Transport and Channel Regulation
- Fetal and Pediatric Neurological Disorders
- Hormonal Regulation and Hypertension
- Cerebrospinal fluid and hydrocephalus
- Genetic and Kidney Cyst Diseases
- Vascular Malformations Diagnosis and Treatment
- Intracranial Aneurysms: Treatment and Complications
- Congenital heart defects research
- Craniofacial Disorders and Treatments
- Hedgehog Signaling Pathway Studies
- Ion channel regulation and function
- Genomics and Rare Diseases
- Cleft Lip and Palate Research
- Adrenal and Paraganglionic Tumors
- Congenital Heart Disease Studies
- Intracerebral and Subarachnoid Hemorrhage Research
- RNA regulation and disease
- Prenatal Screening and Diagnostics
- Skin and Cellular Biology Research
- Genomic variations and chromosomal abnormalities
- Magnesium in Health and Disease
- Genetics and Neurodevelopmental Disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Renal function and acid-base balance
- Glioma Diagnosis and Treatment
Yale University
2016-2025
Rockefeller University
2019
Howard Hughes Medical Institute
2008-2018
Oxford University Press (United Kingdom)
2018
University of Tehran
2007
Islamic Azad University, Tehran
2007
University of Social Welfare and Rehabilitation Sciences
2007
Amirkabir University of Technology
2007
University of Utah
2005
Mayo Clinic
2005
Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K + H excretion. Both encode members the WNK family serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase expression. The WNK4 missense, which cluster short, highly conserved segment encoded protein. proteins localize...
Protein coding genes constitute only approximately 1% of the human genome but harbor 85% mutations with large effects on disease-related traits. Therefore, efficient strategies for selectively sequencing complete regions (i.e., “whole exome”) have potential to contribute understanding rare and common diseases. Here we report a method whole-exome coupling Roche/NimbleGen whole exome arrays Illumina DNA platform. We demonstrate ability capture 95% targeted sequences high sensitivity...
Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in near selectivity filter potassium (K(+)) channel KCNJ5 that present 8 22 human APAs studied. Both produce increased sodium (Na(+)) conductance depolarization, which glomerulosa cells produces calcium (Ca(2+)) entry,...
Coronary artery disease (CAD) is the leading cause of death worldwide and commonly caused by a constellation risk factors called metabolic syndrome. We characterized family with autosomal dominant early CAD, features syndrome (hyperlipidemia, hypertension, diabetes), osteoporosis. These traits showed genetic linkage to short segment chromosome 12p, in which we identified missense mutation LRP6 , encodes co-receptor Wnt signaling pathway. The mutation, substitutes cysteine for arginine at...
We describe members of 4 kindreds with a previously unrecognized syndrome characterized by seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (hypokalemia, metabolic alkalosis, hypomagnesemia). By analysis linkage we localize the putative causative gene to 2.5-Mb segment chromosome 1q23.2-23.3. Direct DNA sequencing KCNJ10, which encodes an inwardly rectifying K(+) channel, identifies unidentified missense or nonsense mutations on both alleles in all...
Nonalcoholic fatty liver disease is associated with hepatic insulin resistance and type 2 diabetes mellitus. Whether this association has a genetic basis unknown.In 95 healthy Asian Indian men, group known to have high prevalence of nonalcoholic disease, we genotyped two single-nucleotide polymorphisms (SNPs) in the gene encoding apolipoprotein C3 (APOC3) that are be hypertriglyceridemia (rs2854116 [T-455C] rs2854117 [C-482T]). Plasma concentrations, sensitivity, triglyceride content were...
Hypertension and dyslipidemia are risk factors for atherosclerosis occur together more often than expected by chance. Although this clustering suggests shared causation, unifying remain unknown. We describe a large kindred with syndrome including hypertension, hypercholesterolemia, hypomagnesemia. Each phenotype is transmitted on the maternal lineage pattern indicating mitochondrial inheritance. Analysis of genome identified homoplasmic mutation substituting cytidine uridine immediately 5'...
Anaplastic thyroid carcinoma (ATC) is a frequently lethal malignancy that often unresponsive to available therapeutic strategies. The tumorigenesis of ATC and its relationship the widely prevalent well-differentiated carcinomas are unclear. We have analyzed 22 cases as well 4 established cell lines using whole-exome sequencing. A total 2674 somatic mutations (121/sample) were detected. Ontology analysis revealed majority variants aggregated in MAPK, ErbB RAS signaling pathways. Mutations...
Many Mendelian traits are likely unrecognized owing to absence of traditional segregation patterns in families due causation by de novo mutations, incomplete penetrance, and/or variable expressivity. Genome-level sequencing can overcome these complications. Extreme childhood phenotypes promising candidates for new traits. One example is early onset hypertension, a rare form global cause morbidity and mortality. We performed exome 40 unrelated subjects with hypertension primary aldosteronism...
We recently implicated two recurrent somatic mutations in an adrenal potassium channel, KCNJ5, as a cause of aldosterone-producing adenomas (APAs) and one inherited KCNJ5 mutation Mendelian form early severe hypertension with massive hyperplasia. The identified all altered the channel selectivity filter, producing increased Na + conductance membrane depolarization, signal for aldosterone production proliferation glomerulosa cells. report herein members four kindreds onset primary...
Premature fusion of the cranial sutures (craniosynostosis), affecting 1 in 2000 newborns, is treated surgically infancy to prevent adverse neurologic outcomes. To identify mutations contributing common non-syndromic midline (sagittal and metopic) craniosynostosis, we performed exome sequencing 132 parent-offspring trios 59 additional probands. Thirteen probands (7%) had damaging de novo or rare transmitted SMAD6, an inhibitor BMP - induced osteoblast differentiation (p<10-20). SMAD6...