Kedous Y. Mekbib
A5089242485- Fetal and Pediatric Neurological Disorders
- Cerebrospinal fluid and hydrocephalus
- Genomic variations and chromosomal abnormalities
- Intracranial Aneurysms: Treatment and Complications
- Genetic and Kidney Cyst Diseases
- Vascular Malformations Diagnosis and Treatment
- Prenatal Screening and Diagnostics
- Genomics and Rare Diseases
- Chromatin Remodeling and Cancer
- Genetics and Neurodevelopmental Disorders
- Hedgehog Signaling Pathway Studies
- Tuberous Sclerosis Complex Research
- Diversity and Career in Medicine
- Barrier Structure and Function Studies
- Click Chemistry and Applications
- Congenital gastrointestinal and neural anomalies
- Moyamoya disease diagnosis and treatment
- Intracerebral and Subarachnoid Hemorrhage Research
- Genetic Associations and Epidemiology
- PI3K/AKT/mTOR signaling in cancer
- Cardiac, Anesthesia and Surgical Outcomes
- interferon and immune responses
- Chemical Synthesis and Analysis
- Surgical Simulation and Training
- Spinal Dysraphism and Malformations
Massachusetts General Hospital
2022-2025
Harvard University
2022-2025
Yale University
2020-2025
Dartmouth College
2024
University of Ottawa
2017
Abstract To elucidate the pathogenesis of vein Galen malformations (VOGMs), most common and severe congenital brain arteriovenous malformations, we performed an integrated analysis 310 VOGM proband-family exomes 336,326 human cerebrovasculature single-cell transcriptomes. We found Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10 −7 ). Rare, damaging transmitted were enriched in Ephrin receptor-B4...
Congenital hydrocephalus, characterized by cerebral ventriculomegaly, is one of the most common reasons for paediatric brain surgery. Recent studies have implicated lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) as a candidate congenital hydrocephalus risk gene; however, TRIM71 variants not been systematically examined in large patient cohort or conclusively linked with an OMIM syndrome. Through cross-sectional analysis largest assembled patients including neurosurgically-treated...
INTRODUCTION: Chiari malformation type 1 (CM1) is the most common disorder of craniocervical junction characterized by herniation cerebellar tonsils causing compression neural tissue and obstruction CSF flow. Despite its prevalence, our poor understanding molecular pathogenesis has contributed to significant variability in clinical surgical outcomes. METHODS: We performed WES 1585 patient-parent trios identify de novo variants (DNVs) uncover exome-wide high-confidence CM1 genes. Integrative...
Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), cardinal feature congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD).
Arachnoid cysts (ACs) are the most common space-occupying lesions in human brain and present significant challenges for clinical management. While cases of ACs sporadic, nearly 40 familial forms have been reported. Moreover, seen with increased frequency multiple Mendelian syndromes, including Chudley-McCullough syndrome, acrocallosal autosomal recessive primary ciliary dyskinesia. These findings suggest that genetic factors contribute to AC pathogenesis. However, traditional linkage...
Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery in children. Recent studies have implicated SMARCC1, a component of BRG1-associated factor (BAF) chromatin remodelling complex, as candidate congenital hydrocephalus gene. However, SMARCC1 variants not been systematically examined large patient cohort or conclusively linked with human syndrome. Moreover, hydrocephalus-associated functionally validated mechanistically studied vivo....
To elucidate the pathogenesis of vein Galen malformations (VOGMs), most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis 310 VOGM proband-family exomes 336,326 human cerebrovasculature single-cell transcriptomes. We found Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden loss-of-function de novo variants (p=4.79×10 -7 ). Rare, damaging transmitted were enriched in Ephrin receptor-B4 EPHB4 (p=1.22×10 -5 ), which...
In 2019, the American Association of Medical Colleges (AAMC) identified discipline medical humanities as a priority in education. Although programs have existed and osteopathic schools U.S. Canada since late 1960's, this interdisciplinary field remains difficult to define. We studied mission statements identify core themes priorities.We conducted content analysis MD DO associated descriptions (n = 56). compared across whose directors had clinical degree versus terminal research degree,...
INTRODUCTION: Fetal ventriculomegaly, the most common antenatally-diagnosed brain abnormality, is defining feature of congenital hydrocephalus (CH). ventriculomegaly also an overlooked associated finding in neuropsychiatric disorders, including autism spectrum disorder (ASD), which diagnosed at a 10-fold higher rate CH patients than general population. METHODS: We subjected 2,978 parent-trio probands with primary shunted, sporadic CH, to whole exome sequencing (WES). Using mouse molecular...
Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly (CV), is among the most common and least understood pediatric neurosurgical disorders. In largest-assembled CV cohort (>2,697 parent-proband trios), we identified an exome-wide significant enrichment of protein-altering de novo variants (DNVs) in LDB1 (p = 1.11 x 10-15). Seven unrelated patients with ventriculomegaly, developmental delay, dysmorphic features harbored loss-of-function DNVs that truncate LDB1's...
Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly (CV), is among the most common and least understood pediatric neurosurgical disorders. We have identified in largest-assembled CV cohort (>2,697 parent-proband trios) an exome-wide significant enrichment of protein-altering de novo variants (DNVs) LDB1 (p = 1.11 x 10-15). Eight unrelated patients with ventriculomegaly, developmental delay, dysmorphic features harbored loss-of-function DNVs that truncate LDB1's...
SUMMARY Expansion of the cerebrospinal fluid (CSF)-filled cerebral ventricles (ventriculomegaly) is quintessential feature congenital hydrocephalus (CH) but also seen in autism spectrum disorder (ASD) and several neuropsychiatric diseases. PTEN frequently mutated ASD; here, we show a bona fide risk gene for development ventriculomegaly, including neurosurgically-treated CH. Pten -mutant associated with aqueductal stenosis due to hyperproliferation periventricular Nkx2.1 + neural precursors...
Epigenetics control numerous cellular processes such as gene transcription, signal transduction, and protein stabilization. An understanding of epigenetic mechanisms can lead to the development therapeutic agents for various diseases. Herein, we report design synthesis a sinefungin affinity-probe (BpyneSF) that targets methyltranferase enzymes proteins involved in recognition methylation. This probe contains bioorthogonal alkyne residue conjugation using copper-catalyzed azide–alkyne...
INTRODUCTION: Vein of Galen malformations (VOGM) are rare, potentially lethal brain arteriovenous (AVM). The roles EPHB4, RASA1, and ACVRL1 have been described in VOGM pathogenesis, previous studies reported the co-occurrence with cardiac vascular disorders. METHODS: We queried our cross-institutional cohort 129 patients detailed genotypic phenotypic data. Genetic samples from a subset 114 probands, including 90 trios, underwent whole exome sequencing. RESULTS: found that 9.3% had structural...
INTRODUCTION: Early neurovascular development is a complex and intricate process with devastating consequences when impaired. Vein of Galen Aneurysmal Malformations (VGAMs) are the most common severe neonatal arteriovenous malformation often present high-output heart failure, hydrocephalus, neurodevelopmental delay, brain hemorrhage. Despite their prevalence severity, little known regarding genetic pathomechanism. METHODS: Genetic samples were collected from 114 VGAM probands, including 90...
Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery. A few familial forms of congenital hydrocephalus (CH) have been identified, but cause sporadic cases CH remains elusive. Recent studies implicated