Neuropathological hallmarks of fetal hydrocephalus linked to CCDC88C pathogenic variants
| العنوان: | Neuropathological hallmarks of fetal hydrocephalus linked to CCDC88C pathogenic variants |
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| المؤلفون: | Myriam Vezain, Bruno J. Gonzalez, Florent Marguet, Annie Laquerrière, Nathalie Drouot, Arie Horowitz, Pascale Saugier-Veber, Kévin Cassinari, Pascale Marcorelles, Séverine Audebert-Bellanger, Pascal Chambon |
| المصدر: | Acta Neuropathologica Communications Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-7 (2021) |
| بيانات النشر: | BioMed Central, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Pathology, medicine.medical_specialty, Choroid plexus hydrops, Case Report, Neuropathology, Diaphragmatic defect, Biology, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, Fetus, Multiple ependymal malformations, Pregnancy, Foetal hydrocephalus, medicine, Humans, RC346-429, CCDC88C pathogenic variants, Neural tube defect, Microfilament Proteins, Wnt signaling pathway, Neural tube, Intracellular Signaling Peptides and Proteins, Brain, medicine.disease, Planar cell polarity, Autosomal recessive inheritance, Hydrocephalus, Pedigree, Bilateral Renal Agenesis, Fetal Diseases, medicine.anatomical_structure, Renal agenesis, Mutation, Choroid plexus, Female, Neurology. Diseases of the nervous system, Neurology (clinical), Ventriculomegaly |
| الوصف: | The prevalence of congenital hydrocephalus has been estimated at 1.1 per 1000 infants when including cases diagnosed before 1 year of age after exclusion of neural tube defects. Classification criteria are based either on CSF dynamics, pathophysiological mechanisms or associated lesions. Whereas inherited syndromic hydrocephalus has been associated with more than 100 disease-causing genes, only four genes are currently known to be linked to congenital hydrocephalus either isolated or as a major clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. In the past 10 years, pathogenic variants in CCDC88C have been documented but the neuropathology remains virtually unknown. We report the neuropathology of two foetuses from one family harbouring two novel compound heterozygous pathogenic variants in the CCDC88C gene: a maternally inherited indel in exon 22, c.3807_3809delinsACCT;p.(Gly1270Profs*53) and a paternally inherited deletion of exon 23, c.3967-?_c.4112-?;p.(Leu1323Argfs*10). Medical termination of pregnancy was performed at 18 and 23 weeks of gestation for severe bilateral ventriculomegaly. In both fetuses, brain lesions consisted of multifocal atresia-forking along the aqueduct of Sylvius and the central canal of the medulla, periventricular neuronal heterotopias and choroid plexus hydrops. The second fetus also presented lumbar myelomeningocele, left diaphragmatic hernia and bilateral renal agenesis. CCDC88C encodes the protein DAPLE which contributes to ependymal cell planar polarity by inhibiting the non-canonical Wnt signaling pathway and interacts with MPDZ and PARD3. Interestingly, heterozygous variants in PARD3 result in neural tube defects by defective tight junction formation and polarization process of the neuroepithelium. Besides, during organ formation Wnt signalling is a prerequisite for planar cell polarity pathway activation, and mutations in planar cell polarity genes lead to heart, lung and kidney malformations. Hence, candidate variants in CCDC88C should be carefully considered whether brain lesions are isolated or associated with malformations suspected to result from disorders of planar cell polarity. |
| اللغة: | English |
| تدمد: | 2051-5960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d273b6f70da243ef1ab5c28a62fe021aTest http://europepmc.org/articles/PMC8183048Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d273b6f70da243ef1ab5c28a62fe021a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20515960 |
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