Planar cell polarity gene mutations contribute to the etiology of human neural tube defects in our population

2014 ◽  
Vol 100 (8) ◽  
pp. 633-641 ◽  
Author(s):  
Patrizia De Marco ◽  
Elisa Merello ◽  
Gianluca Piatelli ◽  
Armando Cama ◽  
Zoha Kibar ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Gene Mutations ◽  
Polarity Gene

scholarly journals Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans

2015 ◽  
Author(s):  
J. H. Seo ◽  
Y. Zilber ◽  
S. Babayeva ◽  
J. Liu ◽  
P. Kyriakopoulos ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Polarity Gene

scholarly journals Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans

2011 ◽  
Vol 20 (22) ◽  
pp. 4324-4333 ◽  
Author(s):  
J. H. Seo ◽  
Y. Zilber ◽  
S. Babayeva ◽  
J. Liu ◽  
P. Kyriakopoulos ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Polarity Gene

Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis

2012 ◽  
Vol 94 (3) ◽  
pp. 176-181 ◽  
Author(s):  
Redouane Allache ◽  
Patrizia De Marco ◽  
Elisa Merello ◽  
Valeria Capra ◽  
Zoha Kibar
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Polarity Gene

scholarly journals Neuropathological hallmarks of fetal hydrocephalus linked to CCDC88C pathogenic variants

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Florent Marguet ◽  
Myriam Vezain ◽  
Pascale Marcorelles ◽  
Séverine Audebert-Bellanger ◽  
Kévin Cassinari ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Wnt Signaling Pathway ◽  
Brain Lesions ◽  
Congenital Hydrocephalus ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Defects Classification

AbstractThe 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.

scholarly journals Vangl2-environment interaction causes severe neural tube defects, without abnormal neuroepithelial convergent extension

2021 ◽  
Author(s):  
Oleksandr Nychyk ◽  
Gabriel L. Galea ◽  
Matteo Molè ◽  
Dawn Savery ◽  
Nicholas D.E. Greene ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Cell Polarity ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Gene Mutations ◽  
Positive Control ◽  
Mouse Embryos ◽  
Environment Interaction ◽  
Convergent Extension ◽  
Partial Loss

Planar cell polarity (PCP) signalling is vital for initiation of mouse neurulation, with diminished convergent extension (CE) cell movements leading to craniorachischisis, a severe neural tube defect (NTD). Some humans with NTDs also have PCP gene mutations but these are heterozygous, not homozygous as in mice. Other genetic or environmental factors may interact with partial loss of PCP function in human NTDs. We found that reduced sulfation of glycosaminoglycans interacts with heterozygosity for the Lp allele of Vangl2 (a core PCP gene), to cause craniorachischisis in cultured mouse embryos, with rescue by exogenous sulphate. We hypothesised this glycosaminoglycan-PCP interaction may regulate CE but, surprisingly, DiO labeling of the embryonic node demonstrates no abnormality of midline axial extension in sulfation-depleted Lp/+ embryos. Positive-control Lp/Lp embryos show severe CE defects. Abnormalities were detected in the size and shape of somites that flank the closing neural tube in sulfation-depleted Lp/+ embryos. We conclude that failure of closure initiation can arise by a mechanism other than faulty neuroepithelial CE, with possible involvement of matrix-mediated somite expansion, adjacent to the closing neural tube.

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