STUDY DESIGN: A single large family, in which adolescent idiopathic scoliosis 
(AIS) and pectus excavatum (PE) segregate as an autosomal dominant condition, 
was evaluated. Genome-wide linkage analysis and candidate gene sequencing were 
performed.
OBJECTIVE: To map the disease-causing locus in a large white family in which AIS 
and PE cosegregate.
SUMMARY OF BACKGROUND DATA: AIS and PE are common musculoskeletal conditions 
known to have a genetic component, though few genes have been identified for 
either. Genetic studies have been confounded by a lack of large families in 
which the disorders segregate.
METHODS: Clinical examinations were performed on the proband, who underwent 
posterior spinal fusion, and 12 additional affected family members. To map a 
gene causing AIS and PE, a genome-wide linkage analysis was performed with the 
Affymetrix Mapping 10 K XbaI array on 13 affected and 10 unaffected family 
members. Candidate genes were sequenced.
RESULTS: AIS was present in 13 female family members and PE was present in 3 
males and 1 female. Genome-wide linkage analysis resulted in a linkage peak on 
chromosome 18 q with a maximum parametric multipoint logarithm of the odds score 
of 3.86. Recombinants delineated the critical genetic region to an interval of 
6.4 cM between SNP_A-1519369 and SNP_A-1507702, corresponding to a 7.06-Mb 
region (hg18: chr18:26342508-34395660). The chromosome 18 q linkage region 
contains more than 30 genes. Resequencing of the coding regions of 21 candidate 
genes in the region did not reveal any causative mutation.
CONCLUSION: Linkage analysis in this large family demonstrated a novel locus for 
AIS and PE on chromosome 18 q. Because of the increased frequency of PE in 
family members of AIS patients, consideration of family members with PE as 
affected may increase the power of AIS genetic linkage studies.