Males With Familial Idiopathic Scoliosis

Abstract

Study Design Statistical analysis of genomic screening and fine mapping data. Objective The goals of this study were to analyze a region on chromosome 17 and to identify specific genetic determinants within this region linked to familial idiopathic scoliosis (FIS) in a subgroup of families in which affected males have undergone surgery. Summary of Background Data The high prevalence and variability of FIS is indicative of genetic heterogeneity. To localize genes related to scoliosis, identification of groups of families with common clinical characteristics is a strategy that reduces genetic heterogeneity. Two independent studies have implicated a region on chromosome 17 as related to FIS. Methods With approval of the Institutional Review Board, the initial study population consisted of 202 families (1198 individuals), each of which had 2 or more affected individuals; 17 of those families had an affected male who had surgery. Individuals underwent genomic screening and subsequent fine mapping. Results were obtained using model-independent linkage analysis, with scoliosis set as a qualitative and as a quantitative trait, as implemented in SIBPAL (S.A.G.E., v4.5). The level of significance was set at P ≤ 0.05. Results The initial study population had significant results at markers d17s975 and d17s2196. Analyses of a subgroup of families with males having undergone surgery using a customized single nucleotide polymorphism panel resulted in increased significance of this region. Conclusion The data confirm a previously reported genetic locus on chromosome 17 as statistically significant in the etiology of FIS within a subgroup of families in which an affected male had spinal surgery.

Polimorfismo do gene da eca e da α-actinina 3 na escoliose idiopática do adolescente

“…This study mapped a region of approximately 20 cm on chromosome 17p11 linked to idiopathic scoliosis. Another study conducted by Clough et al, 11 in 2010, confirmed, by means of the linkage study, the relationship between the region described by Salehi et al 9 and familial idiopathic scoliosis, when studying 17 families with one member (proband) affected, of the male sex, who required surgical treatment to correct the deformity. Ocaka et al found chromosomal regions in chromosomes 9q34 and 17q25 2 …”

Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis

“…We performed exome sequencing for a multigenerational family with familial IS and identified a potentially damaging and rare variant in the HSPG2 gene. Our previous linkage results were reviewed for potential correlation with the location of newly identified variants ( Miller et al 2005 , 2006 ; Alden et al 2006 ; Clough et al 2010 ; Marosy et al 2010 ). When this particular family was analyzed individually, marginal linkage signals were noted at nine loci (Miller, unpublished data, 2014).…”

“…The current literature includes multiple studies that have used linkage and association analyses. Genome-wide linkage analyses have effectively localized candidate regions; however, progress has been burdened by heterogeneity both within and between study populations and by insufficient statistical power ( Wise et al 2000 ; Chan et al 2002 ; Salehi et al 2002 ; Justice et al 2003 ; Miller et al 2005 , 2006 ; Alden et al 2006 ; Ocaka et al 2008 ; Gurnett et al 2009 ; Raggio et al 2009 ; Clough et al 2010 ; Marosy et al 2010 ; Edery et al 2011 ). Association studies, including genome-wide association studies (GWAS), have implicated select genes, including CHD7 , LBX1 , and GPR126 ( Gao et al 2007 ; Sharma et al 2011 ; Takahashi et al 2011 ; Kou et al 2013 ).…”

Adolescent idiopathic scoliosis: current concepts on neurological and muscular etiologies

“…Using this technique, Wise et al [ 14 ] in 2000, described the first regions related to AIS, on chromosomes 6p, 10q and 18q, after studying a large family with seven members affected by this disease. In the following years, other family studies have suggested that adolescent idiopathic scoliosis were related to chromosomes 6, 9, 16 and 17 [ 41 ], 17p11 [ 42 ], 19p13.37 [ 43 ], 8q12 [ 44 ], 9q31-q34.2 and 17q25.3-qtel [ 1 ], 12p23 [ 45 ] and 18q12.1-12.2 [ 46 ]. Wajchenberg et al [ 47 ] found no connection when studied a Brazilian family with multiple affected members.…”