par Jacquemin, Valérie 
;Antoine, Mathieu ;Duerinckx, Sarah ;Massart, Annick ;Désir, Julie ;Perazzolo, Camille ;Cassart, Marie ;Thomas, Dominique;Segers, Valérie ;Lecomte, Sophie ;Abramowicz, Marc ;Pirson, Isabelle
Référence Human molecular genetics
Publication Publié, 2020-11-01
;Antoine, Mathieu ;Duerinckx, Sarah ;Massart, Annick ;Désir, Julie ;Perazzolo, Camille ;Cassart, Marie ;Thomas, Dominique;Segers, Valérie ;Lecomte, Sophie ;Abramowicz, Marc ;Pirson, Isabelle Référence Human molecular genetics
Publication Publié, 2020-11-01
Article révisé par les pairs
| Résumé : | 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. |
