Planar cell polarity gene mutations contribute to the etiology of human neural tube defects in our population.
Neural Tube Defects (NTDs) are congenital malformations that involve failure of the neural tube closure during the early phases of development at any level of the rostro-caudal axis. The planar cell polarity (PCP) pathway is a highly conserved, noncanonical Wnt-Frizzled-Dishevelled signaling cascade, that was first identified in the fruit fly Drosophila. We are here reviewing the role of the PCP pathway genes in the etiology of human NTDs, updating the list of the rare and deleterious mutations identified so far. We report 50 rare nonsynonymous mutations of PCP genes in 54 patients having a pathogenic effect on the protein function. Thirteen mutations that have previously been reported as novel are now reported in public databases, although at very low frequencies. The mutations were private, mostly missense, and transmitted by a healthy parent. To date, no clear genotype-phenotype correlation has been possible to create. Even if PCP pathway genes are involved in the pathogenesis of neural tube defects, future studies will be necessary to better dissect the genetic causes underlying these complex malformations.
Istituto Giannina Gaslini, Genova, Italy.
Patrizia
P
De Marco
Elisa
E
Merello
Gianluca
G
Piatelli
Armando
A
Cama
Zoha
Z
Kibar
Valeria
V
Capra
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors / Q000235:genetics; D006801:Humans; D009154:Mutation; D054259:Neural Tube / Q000196:embryology*; D009436:Neural Tube Defects / Q000235:genetics*; D054261:Neurulation / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D010750:Phosphoproteins; D051153:Wnt Proteins; C000606588:dsh protein, Drosophila
CELSR1 gene; FUZZY gene; FZD3 and FZD6 genes; LRP6 gene; PRICKLE gene; VANGL1 and VANGL2 genes; neural tube defects (NTDs); planar cell polarity pathway (PCP)