Background: The short stature homeobox-containing (SHOX) gene, located in the telomeric pseudoautosomal region 1 (PAR1) on the short arm of both sex chromosomes, is important for linear growth.
Objective and hypotheses: The aim of our study was to evaluate the presence of SHOX gene deletions/point mutations in children with short stature in order to understand the role of SHOX gene in idiopathic short stature (ISS) and estimate its frequency.
Method: This study supported by the Eli Lilly Italia and approved by the Italian Society for Pediatric Endocrinology and Diabetes (ISPED), is a multicenter study involving several Italian Pediatric Endocrinology Units. Out of a total number of 184 blood samples received, 128 were from patients with ISS. Genomic DNA was extracted and used for multiplex ligation-dependent probe amplification (MLPA) and sequencing analysis. MLPA was performed using the SALSA MLPA P018-F1 SHOX probemix kit.
Results: Out of the 160 patients analyzed, ten presented a deletion of the SHOX gene. Among the remaining 150 patients, i) two patients showed deletion of two probes in the putative SHOX regulatory region, ii) one showed deletion of three probes in PAR1, and iii) six showed CRLF2 gene alterations. Three patients had a complex karyotype. Only two patients, with no suggestive clinical signs except for short stature, presented a point mutation in exon 3 (c.367A>G) and in exon 6 (c.701C>T) respectively. The WT genotype was present in 74 patients while for the remaining patients analysis is ongoing.
Conclusion: If we exclude the patients with Leri-Weill syndrome who presented a SHOX gene deletion in 5.4%, in our cohort of patients with ISS the incidence of SHOX gene point mutations was very low (1.5%), suggesting that the presence of mesomelia, minor skeletal abnormalities, and eventually subtle radiographic signs are essential for requiring genetic analysis properly.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology