Lack of evidence of WNT3A as a candidate gene for congenital vertebral malformations

A pilot study was performed using a cohort of patients with congenital vertebral malformations spanning the entire vertebral column was characterized. DNA sequence analysis of the WNT3A gene in these 50 patients with congenital vertebral malformations was performed.A female patient of African ancestry with congenital scoliosis and a T12-L1 hemivertebrae was found to be heterozygous for a missense variant resulting in the substitution of alanine by threonine at codon 134 in highly conserved exon 3 of the WNT3A gene. This variant was found at a very low prevalence (0.35%) in a control population of 443 anonymized subjects and 1.1% in an African population.These data suggest that WNT3A does not contribute towards the development of congenital vertebral malformations. Factors such as phenotypic and genetic heterogeneity may underlie our inability to detect mutations in WNT3A in our patient sample.Congenital vertebral malformations are phenotypically and etiologically heterogeneous. Their estimated incidence is between 0.5 to 1/1000 [1-4]. Vertebral malformations may represent an isolated finding, occur in association with other renal, cardiac, or spinal cord malformations, or occur as part of an underlying chromosome abnormality or syndrome. These include, but are not limited to, hemifacial microsomia, Alagille, Jarcho-Levin, Klippel-Feil, Goldenhar,, basal cell nevus, trisomy 18, diabetic embryopathy and VACTERL (vertebral, cardiac, renal, limb anomalies, anal atresia, tracheo-esophageal fistula) syndromes. Vertebral malformations most commonly include hemivertebrae, vertebral bars, supernumerary vertebrae, butterfly vertebrae, and wedge-shaped vertebrae.Congenital scoliosis is caused by segmentation defects such as fused vertebrae, vertebral body formation defects, and mixed defects in which both types of lesions are encountered [3,4]. Each of these conditions may cause development of a spinal curve based on asymmetric growth. The severity of the curve is related to t