A5051173402- Genomics and Rare Diseases
- Connective tissue disorders research
- Genomic variations and chromosomal abnormalities
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Congenital heart defects research
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- Hereditary Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Congenital Ear and Nasal Anomalies
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Biomedical Text Mining and Ontologies
- HIV/AIDS drug development and treatment
- Oral and gingival health research
- Vascular Malformations and Hemangiomas
- Prenatal Screening and Diagnostics
- Hedgehog Signaling Pathway Studies
- Cancer-related gene regulation
University of Michigan
2016-2025
Michigan Medicine
2021-2023
Pediatrics and Genetics
2019-2022
University of Exeter
2022
C. S. Mott Children's Hospital
2019-2021
Seattle Children's Hospital
2009-2017
University of Washington
2003-2013
University of Oxford
2013
Ghent University Hospital
2009
Seattle University
2008
Abstract Kabuki syndrome is a rare, multiple malformation disorder characterized by distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of reported with syndrome, but parent‐to‐child transmission in more than half‐dozen instances indicates that it an autosomal dominant disorder. We recently caused mutations MLL2 , gene encodes Trithorax‐group histone methyltransferase, protein...
Although biallelic mutations in non-collagen genes account for <10% of individuals with osteogenesis imperfecta, the characterization these has identified new pathways and potential interventions that could benefit even those type I collagen genes. We FKBP10, which encodes 65 kDa prolyl cis–trans isomerase, FKBP65, 38 members 21 families OI. These include 10 from Samoan Islands who share a founder mutation. Of mutations, three are missense; remainder either introduce premature termination...
Transforming growth factor-β (TGF-β) signaling is critical for the differentiation of smooth muscle cells (SMCs) into quiescent expressing a full repertoire contractile proteins. Heterozygous mutations in TGF-β receptor type II (TGFBR2) disrupt and lead to genetic conditions that predispose thoracic aortic aneurysms dissections (TAADs). The aim this study determine molecular mechanism by which TGFBR2 cause TAADs.Using SMCs explanted from patients with mutations, we show decreased expression...
Abstract Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, similar deletions have been identified in individuals developmental delay dysmorphic features. We 34 probands exonic following referral clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum deletions, we report features 27 who represent 23 these families. The frequency among our postnatally diagnosed patients...
Pathogenic variants in KCNB1, encoding the voltage-gated potassium channel KV 2.1, are associated with developmental and epileptic encephalopathy (DEE). Previous functional studies on a limited number of KCNB1 indicated range molecular mechanisms by which affect function, including loss voltage sensitivity, ion selectivity, reduced cell-surface expression.We evaluated series 17 DEE or other neurodevelopmental disorders (NDDs) to rapidly ascertain dysfunction using high-throughput assays....
Hypotonia is characterized by reduced resistance to passive range of motion in joints versus weakness, which a reduction the maximum muscle power that can be generated. (Dubowitz, 1985; Crawford, 1992; Martin, 2005) Based on strong research evidence, central hypotonia accounts for 60% 80% cases hypotonia, whereas peripheral cause about 15% 30% cases. Disorders causing often are associated with depressed level consciousness, predominantly axial normal strength accompanying and hyperactive or...
X-linked intestinal pseudo-obstruction, a rare disorder caused by mutations in FLNA, the gene encoding cytoskeletal protein filamin A, has been regarded as hereditary enteric neuropathy largely on basis of sparse and incomplete pathologic studies. Diffuse abnormal layering small smooth muscle (DAL) is malformation, which only described 4 patients (all male, 3 same family) with pseudo-obstruction. We report DAL 5 male (2 families) pseudo-obstruction FLNA. Light microscopic, ultrastructural,...
De novo truncating mutations in Additional sex combs-like 3 (ASXL3) have been identified individuals with Bainbridge–Ropers syndrome (BRS), characterized by failure to thrive, global developmental delay, feeding problems, hypotonia, dysmorphic features, profound speech delays and intellectual disability. We three novel de heterozygous variants distributed across ASXL3, outside the original cluster of ASXL3 previously described for BRS. Primary skin fibroblasts established from a BRS patient...
Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of fingers, wrists, ankles. Although more than 20 different dominant have been identified myopathy patients, biosynthetic consequences only subset these studied, many cases, pathogenic mechanisms remain unknown.We screened fourteen patients for performed detailed analyses biosynthesis intracellular extracellular assembly.Collagen...
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder that manifests as recurrent, episodic, painful brachial neuropathies. A gene for HNA maps to chromosome 17q25.3 where mutations in SEPT9, encoding the septin-9 protein, have been identified.To determine frequency and type of SEPT9 a new cohort 42 unrelated pedigrees.DNA sequencing all exons intron-exon boundaries was carried out affected individual each pedigree from our cohort. Genotyping using microsatellite markers...
Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 had detailed breakpoint analysis.To further delineate the features of syndrome, clinical molecular characterisation fifteen with deletions in region was performed, nearly doubling number reported patients.Breakpoints were using custom, high-density array comparative...
We describe the molecular and clinical characterization of nine individuals with recurrent, 3.4-Mb, de novo deletions 3q13.2–q13.31 detected by chromosomal microarray analysis. All have hypotonia language motor delays; they variably express mild to moderate cognitive delays (8/9), abnormal behavior (7/9), autism spectrum disorders (3/9). Common facial features include downslanting palpebral fissures epicanthal folds, a slightly bulbous nose, relative macrocephaly. Twenty-eight genes map...
The human immunodeficiency viruses (HIVs) types 1 and 2 have similar genetic organization but differ significantly in nucleic acid sequence. Although infection by either agent leads to symptoms of immunodeficiency, recent studies suggest potential differences the time course severity these diseases. In this report, transcriptional regulation induction retroviruses were analyzed. We report that HIV-2 differs from HIV-1: a distinct T-cell activation pathway, triggering CD3 component receptor...
<h3>Background</h3> Genomic copy number variants have been shown to be responsible for multiple genetic diseases. Recently, a duplication in septin 9 (<i>SEPT9</i>) was causal hereditary neuralgic amyotrophy (HNA), an episodic peripheral neuropathy with autosomal dominant inheritance. This identified 12 pedigrees that all shared common founder haplotype. <h3>Methods and results</h3> Based on array comparative genomic hybridisation, we six additional heterogeneous tandem <i>SEPT9</i>...