Sonal Mahida
A5075699471- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Epilepsy research and treatment
- Cellular transport and secretion
- Congenital Heart Disease Studies
- Mitochondrial Function and Pathology
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Lysosomal Storage Disorders Research
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Metabolism and Genetic Disorders
- Craniofacial Disorders and Treatments
- Trypanosoma species research and implications
- Advanced biosensing and bioanalysis techniques
- Microtubule and mitosis dynamics
- Neuroscience of respiration and sleep
- Glycogen Storage Diseases and Myoclonus
- Protein Degradation and Inhibitors
- Folate and B Vitamins Research
Boston Children's Hospital
2019-2025
Harvard University
2021-2025
Kennedy Krieger Institute
2018-2022
Dr. John T. Macdonald Foundation
2022
RWTH Aachen University
2022
Johns Hopkins University
2018-2022
Washington Center
2018
University of Washington
2018
Abstract Objective We evaluated the yield of systematic analysis and/or reanalysis whole exome sequencing (WES) data from a cohort well‐phenotyped pediatric patients with epilepsy and suspected but previously undetermined genetic etiology. Methods identified phenotyped 125 participants epilepsy. Etiology was unexplained at time enrollment despite clinical testing, which included chromosomal microarray (57 patients), gene panel (n = 48), both 28), or WES 8). Clinical diagnoses developmental...
Importance Genomic advances inform our understanding of epilepsy and can be translated to patients as precision diagnoses that influence clinical treatment, prognosis, counseling. Objective To delineate the genetic landscape pediatric utility for with epilepsy. Design, Setting, Participants This cohort study used phenotypic data from medical records treating clinicians at a hospital identify unexplained pediatric-onset Exome sequencing was performed 522 available biological parents, were...
ABSTRACT Haploinsufficiency of SETD5 , which facilitates gene transcription and histone modification, causes intellectual disability. However, the full phenotypic spectrum Disorder is not well characterized. We summarized clinical features participants with enrolled in National Brain Gene Registry (BGR). analyzed data from 13 individuals a molecular diagnosis Disorder, ages 2–37 years, using electronic health records, standardized surveys, direct assessments. also determined number for whom...
SATB2‐associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted case reports small series without in‐depth phenotypic characterization or genotype‐phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals a molecularly confirmed diagnosis...
Abstract SETD1B is a component of histone methyltransferase complex that specifically methylates Lys-4 H3 (H3K4) and responsible for the epigenetic control chromatin structure gene expression. De novo microdeletions encompassing this as well de missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify specific hypermethylation signature associated with loss function in which may be used an marker supporting diagnosis -related diseases. We...
Abstract Developmental epileptic encephalopathies are devastating disorders characterized by intractable seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH 36 cases from 25 families presenting with encephalopathy delay hypotonia. encodes oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component specific proteoglycans glycolipids. Consistent being loss-of-function alleles, show using patients’ primary fibroblasts...
Abstract KIF21B is a kinesin protein that promotes intracellular transport and controls microtubule dynamics. We report three missense variants one duplication in individuals with neurodevelopmental disorders associated brain malformations, including corpus callosum agenesis (ACC) microcephaly. demonstrate, vivo, the expression of specifically recapitulates patients’ abnormalities, microcephaly reduced intra- inter-hemispheric connectivity. establish impede neuronal migration through...
Thousand and one amino-acid kinase 1 (TAOK1) is a MAP3K protein kinase, regulating different mitogen-activated pathways, thereby modulating multitude of processes in the cell. Given recent finding TAOK1 involvement neurodevelopmental disorders (NDDs), we investigated role neuronal function collected cohort 23 individuals with mostly de novo variants to further define associated NDD. Here, provide evidence for an important function, showing that altered expression levels embryonic mouse brain...
Abstract Objective KCNQ2 ‐associated developmental and epileptic encephalopathies (DEE) present with seizures impairments. The relation between functional impairments in affected children the of a specific genetic variant to seizure control remains unknown. Methods Parents documented variants who participated structured, online natural history survey provided information about history, mobility, hand use, communication function, feeding independence. Bivariate analyses were performed...
Abstract Monogenic disorders account for a large proportion of population-attributable risk neurodevelopmental disabilities. However, the data necessary to infer causal relationship between given genetic variant and particular disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual Developmental Disabilities Research Centers (IDDRCs) formed consortium create Brain Gene Registry (BGR), repository pairing clinical with phenotypic from participants variants in putative...
Neurodevelopmental disorders are genetically and phenotypically heterogeneous encompassing developmental delay (DD), intellectual disability (ID), autism spectrum (ASDs), structural brain abnormalities, neurological manifestations with variants in a large number of genes (hundreds) associated. To date, few de novo mutations potentially disrupting TCF20 function patients ID, ASD, hypotonia have been reported. encodes transcriptional co-regulator structurally related to RAI1, the...
Abstract Background PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 disruption three patients balanced translocations. In addition, de novo truncating mutations were reported recently. Here, we analyze genomic data from seven unrelated individuals provide detailed clinical descriptions, further expanding phenotype haploinsufficiency. Methods Diagnostic trio whole exome sequencing,...
Genetic variants in KCNQ2 are associated with a range of epilepsies, from self- limited (familial) neonatal-infantile epilepsy to developmental and epileptic encephalopathy (DEE). We retrospectively reviewed clinical data eight patients KCNQ2-related DEE who were treated ezogabine. Treatment was initiated at median age 8 months (range, 7 weeks 2.5 years) continued for 2.6 years 4.5 years). Five individuals had daily seizures baseline experienced least 50% seizure reduction treatment,...
Biallelic pathogenic variants in AARS2, a gene encoding the mitochondrial alanyl-tRNA synthetase, result spectrum of findings ranging from infantile cardiomyopathy to adult-onset progressive leukoencephalopathy. In this article, we present three unrelated individuals with novel compound heterozygous AARS2 underlying diverse clinical presentations. Patient 1 is 51-year-old man cognitive, psychiatric, and motor decline leukodystrophy. 2 34-year-old childhood-onset tremor followed by...
Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates UFMylation pathway of protein modification. UFSP2 variants implicated autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for occurred eight children from four South Asian families with delay epilepsy. describe clinical consequences this its effect on UFMylation.Exome...
PurposeClinically ascertained variants are under-utilized in neurodevelopmental disorder research. We established the Brain Gene Registry (BGR) to coregister clinically identified putative brain genes with participant phenotypes. Here, we report 179 genetic first BGR registrants and analyze proportion that were novel ClinVar at time of entry those absent other disease databases.MethodsFrom 10 academically affiliated institutions, individuals enrolled into BGR. Variants cross-referenced for...
The blood-brain barrier ensures CNS homeostasis and protection from injury. Claudin-5 (CLDN5), an important component of tight junctions, is critical for the integrity barrier. We have identified de novo heterozygous missense variants in CLDN5 15 unrelated patients who presented with a shared constellation features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly recognizable pattern pontine atrophy brain calcifications. All clustered one...
Abstract Despite its promising diagnostic yield, whole exome sequencing (WES) frequently introduces variant(s) of uncertain significance (VUS), which have been speculated to cause parental stress and anxiety. This study aimed explore the psychosocial impact receiving a VUS from pediatric WES on caregivers identify implications for clinical practice. Fourteen telephone interviews were conducted with parents or legal guardians who received results their child's assess understanding result,...