CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects
Year: 2020
Type: article
Abstract: BACKGROUND: Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH forms at the clinical level. METHODS: (MCPH3) were investigated by performing prospective, extensive and systematic clinical, MRI, psychomotor, neurosensory and cognitive examinations under similar conditions. RESULTS: All patients displayed neurosensory defects in addition to microcephaly. Small cochlea with incomplete partition type II was found in all cases and was associated with progressive deafness in 4 of them. Furthermore, the CDK5RAP2 protein was specifically identified in the developing cochlea from human fetal tissues. Microphthalmia was also present in all patients along with retinal pigmentation changes and lipofuscin deposits. Finally, hypothalamic anomalies consisting of interhypothalamic adhesions, a congenital midline defect usually associated with holoprosencephaly, was detected in 5 cases. CONCLUSION: not only governs brain size but also plays a role in ocular and cochlear development and is necessary for hypothalamic nuclear separation at the midline. Our data indicate that CDK5RAP2 should be considered as a potential gene associated with deafness and forme fruste of holoprosencephaly. These children should be given neurosensory follow-up to prevent additional comorbidities and allow them reaching their full educational potential. TRIAL REGISTRATION NUMBER: NCT01565005.
Source: Journal of Medical Genetics
Authors: Hala Nasser, Liza Vera, Monique Elmaleh-Bergès, Katharina Steindl, Pascaline Letard, Natacha Teissier, Anais Ernault, Fabien Guimiot, Alexandra Afenjar, Marie Laure Moutard, Delphine Héron, Yves Alembik, Martha Momtchilova, Paolo Milani, Nathalie Kubis, Nathalie Pouvreau, Marcella Zollino, Sophie Guilmin Crepon, Florentia Kaguelidou, Pierre Gressens, Alain Verloes, Anita Rauch, Vincent El Ghouzzi, Severine Drunat, Sandrine Passemard
Institutions: Assistance Publique – Hôpitaux de Paris, Hôpital Robert-Debré, University of Zurich, Inserm, Université Paris Cité, Université Sorbonne Paris Nord, Hôpital Jean-Verdier, NeuroDiderot, Sorbonne Université, Hôpital Armand-Trousseau, Pitié-Salpêtrière Hospital, Hôpital d'Hautepierre, Hôpital Lariboisière, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Centre d'Investigation Clinique Robert Debré, King's College London, ERN ITHACA
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Implication of the golgi apparatus secretory functions in the developpement Of postnatal microcephaly and intellectual disabilities, Primary monogenic microcephalies : from genetics to pathophysiology and the clinic, Primary monogenic microcephalies: from genetics to pathophysiology and the clinic, Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences
OpenAlex ID: W3005115522