Males with familial idiopathic scoliosis: a distinct phenotypic subgroup.
METHODS
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.


BACKGROUND
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 < or = 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.


CONCLUSIONS
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.
Clough
Mark
M
Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
Justice
Cristina M
CM
Marosy
Beth
B
Miller
Nancy H
NH
D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012600:Scoliosis / Q000235:genetics*