Clinical and molecular characterization of Chilean patients with Léri-Weill dyschondrosteosis

Abstract

Aim: L é ri-Weill dyschondrosteosis (LWD) is a mesomelic dysplasia with disproportionate short stature associated with short stature homeobox-containing gene (SHOX) haploinsufficiency. The objective of this study was to improve the diagnosis of patients with suspected LWD through molecular analysis. Methods: Twelve patients from 11 families with a clinical diagnosis of LWD were analyzed with multiplex ligationdependent probe amplification to detect deletions and duplications of SHOX and its enhancer regions. High resolution melting and sequencing was employed to screen for mutations in SHOX coding exons. Results: The molecular-based screening strategy applied in these patients allowed detection of five SHOX deletions and two previously unreported SHOX missense mutations. Conclusion: Molecular studies confirmed the clinical diagnosis of LWD in seven out of 12 patients, which provided support for therapeutic decisions and improved genetic counseling in their families.