A5061314401- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Blood disorders and treatments
- Wnt/β-catenin signaling in development and cancer
- Folate and B Vitamins Research
- Retinal Development and Disorders
- Neurological diseases and metabolism
- Retinal Diseases and Treatments
- Biochemical and Molecular Research
- Autism Spectrum Disorder Research
- Connexins and lens biology
- Metabolomics and Mass Spectrometry Studies
- Cerebrovascular and genetic disorders
- Genetic Associations and Epidemiology
- Williams Syndrome Research
- Hereditary Neurological Disorders
- Axon Guidance and Neuronal Signaling
Boston Children's Hospital
2014-2024
Harvard University
2016-2024
Children's Hospital Colorado
2024
University of Colorado Denver
2024
Polyamines serve a number of vital functions in humans, including regulation cellular proliferation, intracellular signaling, and modulation ion channels. Ornithine decarboxylase 1 (ODC1) is the rate‐limiting enzyme endogenous polyamine synthesis. In this report, we present four patients with distinct neurometabolic disorder associated de novo heterozygous, gain‐of‐function variants ODC1 gene. This presents global developmental delay, ectodermal abnormalities alopecia, absolute or relative...
Abstract Background We aimed to define the clinical and variant spectrum provide novel molecular insights into DHX30 -associated neurodevelopmental disorder. Methods Clinical genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, our network of collaborators. investigated impact missense variants with respect ATPase helicase activity, stress granule (SG) formation, global translation, their effect on embryonic development in zebrafish....
Abstract Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 T, p.(Arg404*), and c.992 T G, p.(Ile331Ser). The p.(Leu27Argfs*39) change is predicted to result in complete absence MINPP1. p.(Arg404*) would likely lead nonsense mediated...
Semaphorins and plexins are ligands cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth guidance. PLXNA3 is a plexin gene located on the X chromosome encodes most widely expressed receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role semaphorin signaling vivo. The clinical manifestations of semaphorin/plexin disorders have been less explored. This study describes neurological phenotypes boys with maternally inherited...
Abstract Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to large group protein (PP1), major eukaryotic serine/threonine that regulates diverse cellular processes. Here, we describe identification hemizygous variants in PPP1R3F associated with novel X-linked recessive neurodevelopmental disorder 13 unrelated individuals. This characterized by developmental delay, mild intellectual disability, neurobehavioral issues...
ABSTRACT Purpose Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 encodes a core member of the protein complex that methylates histone 3 lysine-4 (H3K4) and not implicated in human disease. Methods We identify five unrelated individuals de novo heterozygous pathogenic variants . Three truncating two missense were identified probands neurodevelopmental symptoms including global developmental delay, intellectual disability, microcephaly, short stature. Here, we...
Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder with variable expressivity in heterozygous females. While liver function testing often abnormal patients OTCD, failure uncommon on presentation. A 13-month-old female no significant past medical history presented irritability, right arm weakness, and decreased appetite. Initial workup revealed hepatic dysfunction INR of 3.4, ammonia level 75 μmol/L, brain MRI gyral edema restricted diffusion, patchy signal...
Best vitelliform macular dystrophy (BVMD) is a slowly progressive disease caused by pathogenic variant of the Bestrophin (BEST1) gene. Examination coupled with multimodal imaging and genetic testing are used to guide diagnosis treatment. A 12-year-old girl was examined for decreased vision in left eye showed bilateral "egg-yolk"-like lesions choroidal neovascularization (CNV) eye. Six months later, she experienced appearance CNV on optical coherence tomography angiography right Injections...
Abstract Introduction There are overlapping features between inflammatory myopathies and muscular dystrophies, particularly laminopathies. Key that characterize laminopathies include axial proximal weakness, contractures, cardiac abnormalities. Methods/Results A 12‐year‐old girl diagnosed with juvenile dermatomyositis as a child presented failure was found to have an LMNA likely pathogenic variant, phenotype most consistent Emery–Dreifuss dystrophy type 2. Discussion The spectrum of clinical...
Graves' disease (GD) is rare in children under age five years. Antithyroid drugs are typically first-line therapy but carry the risks of agranulocytosis and liver dysfunction. A male infant with multiple congenital anomalies, left ventricular hypertrophy, neurologic dysfunction developed GD at months life. The presence chronic hepatitis complicated medical management. Potassium iodide was effective temporarily, urgent thyroidectomy required nine age. Postoperatively, patient a thyroid...
Abstract Introduction: Rapid-onset obesity, hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) is a rare syndrome beginning at 3-6 years of age with approximately 150 cases described. Additional features include eye abnormalities, neurobehavioral paraneoplastic tumors. The etiology the complex phenotype remains unknown. Methods: This study aims to investigate genetic landscape this by whole exome sequencing (WES) copy number variation (CNV) analysis. We recruited...
Purpose: To report a case of 16-month-old boy with novel variant TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in patient familial exudative vitreoretinopathy. Observation: A otherwise healthy was referred to Boston Children’s Hospital for evaluation strabismus. Ocular examination revealed intermittent esotropia, left hypotropia, limited eye elevation both adduction abduction. Full cycloplegic hyperopic correction +3.50 diopters (D) over eyes given the...