Trends in molecular medicine · 2023
Human genetics and molecular genomics of Chiari malformation type 1.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Mekbib Kedous Y, Muñoz William, Allington Garrett, McGee Stephen, Mehta Neel H, Shofi John P, Fortes Carla, Le Hao Thi, Nelson-Williams Carol, Nanda Pranav, Dennis Evan, Kundishora Adam J, Khanna Arjun, Smith Hannah, Ocken Jack, Greenberg Ana B W, Wu Rui, Moreno-De-Luca Andres, DeSpenza Tyrone, Zhao Shujuan, Marlier Arnaud, Jin Sheng Chih, Alper Seth L, Butler William E, Kahle Kristopher T
Аннотация
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.