Introduction: Adolescent idiopathic scoliosis (IS) is the most common spine deformity arising during childhood, but the aetiology of IS remains unknown. A large proportion (75%) of structural scoliosis is clinically classified as idiopathic. Idiopathic scoliosis often appears in several members of the same family, this strongly suggesting a genetic transmission. Clinical studies indicate that approximately 1:4 of the total scoliosis cases and 1:3 of idiopathic scoliosis cases are familial. Also studies on twins showing that concordance of monozygotic twins is greater than that of dizygotic twins suggest a genetic basis for the idiopathic scoliosis. A series of candidate genes, including FBN1, COL1A1, COL1A2, COL2A1 and elastin genes, have already been examined by linkage studies, with negative results, and, at present, the particular mode of inheritance of the idiopathic scoliosis still remains unclear. There are conflicting data in the existing literature. Some reports show that the disorder has many of the characteristics of a complex trait, indicating the presence of a multifactorial inheritance pattern, while other studies indicate a major autosomal dominant gene effect. Even more, not all the linkage studies, which demonstrate that the inheritance pattern of idiopathic scoliosis is based on a major autosomal dominant gene effect, did identify a unique locus responsible for idiopathic scoliosis. A linkage with idiopathic scoliosis has been found at locus 17p11 in a three generation Italian family and at locus 19p13.3 in a Chinese family. Therefore, it is possible that idiopathic scoliosis is caused by alterations in different genes.

Study Design: This study aimed at investigating the loci responsible for susceptibility to idiopathic scoliosis in all the population and not only in single families. For this reason, we chose to perform an association study on parent-offspring trios. A genetic study and statistical linkage analysis of a population of 81 trios, each consisting of a daughter/son affected by idiopathic scoliosis (IS) and both parents.

Objectives: The objective of this study was to assess a linkage disequilibrium between the matrilin-1 (MATN1) gene and the idiopathic scoliosis (IS).

Summary of Background Data: In a previous study (Giampietro et al., 1999), a number of genes, associated with spine musculoskeletal deformity phenotypes in mouse and in synteny between mouse and man, were identified as candidate genes for IS. Among these genes, MATN1, which carries a polymorphic micro-satellite marker within its sequence, was selected for a linkage analysis. MATN1 is localised at 1p35 and is mainly expressed in cartilage.

Methods: In all trios components, the region of MATN1 gene containing the microsatellite marker was amplified by a polymerase chain reaction. The amplicons were analysed by a DNA sequencer-genotyper. The statistical analysis was performed using the extended transmission/disequilibrium test.

Results: Three microsatellite polymorphisms, respectively consisting of 103 bp, 101 bp and 99 bp, were identified. ETDT evidenced a significant preferential transmission for the 103 bp allele (2 = 5.058, df=1, P=0.024).

Main Conclusions: The results suggest that the familial idiopathic scoliosis is linked to the MATN1 gene.