Prevalence of POC5 Coding Variants in French-Canadian and British AIS Cohort.

Hélène Mathieu,Anne Child,Carole Fortin,Florina Moldovan,Stefan Parent,Soraya Barchi,José Antonio Aragon-Martin,Aurélia Spataru

doi:10.3390/genes12071032

Abstract

Adolescent idiopathic scoliosis (AIS) is a complex common disorder of multifactorial etiology defined by a deviation of the spine in three dimensions that affects approximately 2% to 4% of adolescents. Risk factors include other affected family members, suggesting a genetic component to the disease. The POC5 gene was identified as one of the first ciliary candidate genes for AIS, as three variants were identified in large families with multiple members affected with idiopathic scoliosis. To assess the prevalence of p.(A429V), p.(A446T), and p.(A455P) POC5 variants in patients with AIS, we used next-generation sequencing in our cohort of French-Canadian and British families and sporadic cases. Our study highlighted a prevalence of 13% for POC5 variants, 7.5% for p.(A429V), and 6.4% for p.(A446T). These results suggest a higher prevalence of the aforementioned POC5 coding variants in patients with AIS compared to the general population.

Highlights

Adolescent idiopathic scoliosis (AIS) is a common disorder characterized by a combination of deviations of the spine in the sagittal and the coronal plane, with vertebral rotation
Since the identification of POC5 as a candidate gene for adolescent idiopathic scoliosis and its functional validation, we have analyzed the prevalence of POC5 coding variants within the AIS population, and have sought to identify new candidate genes
We reported the prevalence of POC5 gene variants in 13% of AIS patients with or without a family history of this condition; that is, six times more frequent than in our inhouse control cohort that matched for ethnicity

Summary

Introduction

Adolescent idiopathic scoliosis (AIS) is a common disorder characterized by a combination of deviations of the spine in the sagittal and the coronal plane, with vertebral rotation It affects approximatively 3% of the adolescent population [1,2]; affects females more than males, with a ratio ranging from 1.5:1 to 3:1 [2,3]; and is more prevalent in northern latitudes [4]. Since the advent of next-generation sequencing, candidate-gene analysis using pedigrees and population-based genome-wide association studies (GWAS) have been widely used to assess the genetic etiology of AIS. Despite all these efforts, only a few of the candidate genes have been functionally linked to the development of AIS. In 2015, Patten et al [13] performed a linkage analysis followed by exome sequencing, and identified coding variants in the centrosomal protein gene POC5 (NM_001099271) in a multiplex four-generation

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