Human genetics and molecular genomics of Chiari malformation type 1.

Autor: Mekbib KY; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, Massachusetts General Hospital, Boston, MA, USA., Muñoz W; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, Massachusetts General Hospital, Boston, MA, USA., Allington G; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA., McGee S; GeneDx, Gaithersburg, MD, USA., Mehta NH; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Shofi JP; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Fortes C; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Le HT; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Nelson-Williams C; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA., Nanda P; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Dennis E; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Kundishora AJ; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA., Khanna A; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Smith H; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Ocken J; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA., Greenberg ABW; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Wu R; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Moreno-De-Luca A; Department of Radiology, Autism and Developmental Medicine Institute, Genomic Medicine Institute, Geisinger, Danville, PA, USA., DeSpenza T Jr; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA., Zhao S; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA., Marlier A; Altos Labs, San Diego, CA, USA., Jin SC; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA., Alper SL; Division of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA., Butler WE; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Kahle KT; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, Massachusetts General Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: kahle.kristopher@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Trends in molecular medicine [Trends Mol Med] 2023 Dec; Vol. 29 (12), pp. 1059-1075. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1016/j.molmed.2023.08.013
Abstrakt: Chiari malformation type 1 (CM1) is the most common structural brain disorder involving the craniocervical junction, characterized by caudal displacement of the cerebellar tonsils below the foramen magnum into the spinal canal. Despite the heterogeneity of CM1, its poorly understood patho-etiology has led to a 'one-size-fits-all' surgical approach, with predictably high rates of morbidity and treatment failure. In this review we present multiplex CM1 families, associated Mendelian syndromes, and candidate genes from recent whole exome sequencing (WES) and other genetic studies that suggest a significant genetic contribution from inherited and de novo germline variants impacting transcription regulation, craniovertebral osteogenesis, and embryonic developmental signaling. We suggest that more extensive WES may identify clinically relevant, genetically defined CM1 subtypes distinguished by unique neuroradiographic and neurophysiological endophenotypes.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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