Methods of screening for compounds for use as modulators of left-right asymmetry in scoliotic subjects and for monitoring efficacy of an orthopaedic device

A method of monitoring efficacy of an orthopaedic device in a subject having adolescent idiopathic scoliosis (AIS) comprising a) measuring expression of at least one of Nodal, Notch1, Pitx2, Lefty1 and Lefty2 in a sample of paraspinal muscle cells from at least one side of the apex of the main scoliosis curve of the subject before having installed the device on the subject;

• and b) repeating the measure of step a) after having installed the device on the subject, wherein a difference of expression of at least one of Nodal, Notch1, Pitx2, Lefty1 and Lefty2 between steps a) and b) provides an indication on the efficacy of the device.

A method of identifying at least one mutation directly or indirectly contributing to adolescent idiopathic scoliosis (AIS), comprising comparing the nucleotide sequence of a gene of at least one of Nodal, Notch 1, lefty1, Lefty2 and Pitx2 from a subject having AIS with that of the corresponding gene in a control subject, wherein the presence of a mutation in the gene of the subject is an indication that the mutation contributes to AIS.

A method for identifying at least one mutation directly or indirectly contributing to adolescent idiopathic scoliosis (AIS), comprising analyzing (i) the sequence of a gene whose product directly or indirectly modulates Nodal, Notch1, Pitx2, Lefty1 and/or Lefty2's expression, wherein the gene is from a subject having AIS, or (ii) analyzing the sequence of the gene's product, wherein the presence of a mutation in the gene or in the gene's product is an indication that the mutation contributes to AIS in the subject.