Supplementary Material for: Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population

<p><b><i>Background:</i></b> The aim of our study was to describe a large population with anomalies involving the <i>SHOX</i> region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. <b><i>Methods:</i></b> We performed a retrospective multicenter study on French subjects with a <i>SHOX</i> region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for <i>SHOX</i> analysis. <b><i>Results:</i></b> Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either <i>SHOX</i> or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. <b><i>Conclusions:</i></b> Our results highlight genotype-phenotype relationships in the French population with a <i>SHOX</i> defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions.</p>