TrkA mediates effect of novel KIDINS220 mutation in human brain ventriculomegaly
| Autor: | Valérie Jacquemin, Valérie Segers, Marc Abramowicz, Annick Massart, Sarah Duerinckx, Isabelle Pirson, Camille Perazzolo, Dominique Thomas, Mathieu Antoine, Julie Désir, Marie Cassart, Sophie Lecomte |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Pathology medicine.medical_specialty Autopsy Nerve Tissue Proteins Biology medicine.disease_cause Nervous System Malformations 03 medical and health sciences 0302 clinical medicine Fetus Genetics medicine Humans Receptor trkA Molecular Biology Genetics (clinical) 030304 developmental biology 0303 health sciences Mutation Homozygote Brain Mass Membrane Proteins General Medicine Human brain Sciences bio-médicales et agricoles medicine.disease Phenotype Pedigree Chemistry Transmembrane domain medicine.anatomical_structure Female Human medicine 030217 neurology & neurosurgery Ventriculomegaly Hydrocephalus |
| Zdroj: | Human molecular genetics |
| ISSN: | 0964-6906 |
| Popis: | Congenital hydrocephalus is a potentially devastating, highly heterogeneous condition whose genetic subset remains incompletely known. We here report a consanguineous family where three fetuses presented with brain ventriculomegaly and limb contractures, and shared a very rare homozygous variant of KIDINS220, consisting of an in-frame deletion of three amino acids adjacent to the fourth transmembrane domain. Fetal brain imaging and autopsy showed major ventriculomegaly, reduced brain mass, and with no histomorphologic abnormalities. We demonstrate that binding of KIDINS220 to TrkA is diminished by the deletion mutation. This family is the second that associates a KIDINS220 genetic variant with human ventriculomegaly and limb contractures, validating causality of the gene and indicating TrkA as a likely mediator of the phenotype. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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