ESPE Abstracts (2014) 82 P-D-1-1-147

The Role of SHOX Gene in Idiopathic Short Stature: an Italian Multicenter Study

R Minaria, A Votteroa, S Azzolinib, D Barbaroc, G Bindid, M Bozzolae, C Burraif, G M Cardinaleg, D Cioffih, M Cisterninoi, M S Cocciolij, M Delvecchiok, E Fabbrizil, M Ferrarim, F Gallarottin, F Galloo, L Ghizzonip, M C Maggioq, B Mainettir, R Montinaros, G Municchit, A Panariellou, M Parpagnoliv, L Perronew, M Petrarolix, G Radettiy, A F Radicioniz, A RossodivitaA, MC SalernoB, S Savastai, S Seminarav, L TafiC, M TomatD, A TummoloE, M WasniewskaF, L IughettiG & S Bernasconia


aDepartment of Clinical and Experimental Medicine, University of Parma, Parma, Italy; bPediatric Endocrinology and Adolescence Unit, Pediatric Department, University Hospital of Padua, Padua, Italy; cASL 6, Section of Endocrinology, Livorno, Italy; dUnit of Pediatrics, Pistoia Hospital, Pistoia, Italy; eUnit of Auxology, San Matteo Hospital, Pavia, Italy; fEndocrinology Unit, University Hospital of Sassari, Sassari, Italy; gUnit of Pediatrics, Ferrari Hospital, Casarano (LE), Italy; hAuxology and Endocrinology Units, Santobono Pausilipon Hospital, Naples, Italy; iUnit of Pediatrics, San Matteo Hospital, Pavia, Italy; jUnit of Pediatrics, Camberlingo Hospital, Francavilla Fontana (BR), Italy; kPediatrics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; lUnit of Pediatrics, Civili Hospital, Fermo, Italy; mAUSL 1, Department of Pediatrics, Massa Carrara, Italy; nDepartment of Pediatrics, S. Croce e Carle Hospital, Cuneo, Italy; oUnit of Pediatrics, Perrino Hospital, Brindisi, Italy; pDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy; qUnit of Pediatrics, G.Di Cristina Hospital, Palermo, Italy; rUnit of Pediatrics, AUSL, Forlì, Italy; sUnit of Pediatrics, S. Caterina Novella Hospital, Galatina (LE), Italy; tPediatric Department, University of Siena, Siena, Italy; uDepartment of Pediatrics, San Salvatore Hospital, Pesaro, Italy; vDepartment of Pediatrics, Meyer Children Hospital, Florence, Italy; wPediatric 2 Unit Department Donna, Bambino e Chirurgia Generale e Specialistica, Second University of Naples, Naples, Italy; xUnit of Pediatrics, Santa Maria Nuova Hospital, Reggio Emilia, Italy; yDepartment of Pediatrics, Regional Hospital, Bolzano, Italy; zDepartment of Experimental Medicine, Sapienza University, Rome, Italy; ADepartment of Pediatrics, UCSC, Rome, Italy; BDepartment of Pediatrics, Federico II University, Naples, Italy; CAUSL 8, Department of Pediatrics, Arezzo, Italy; DUnit of Pediatrics, University Hospital of Udine, Udine, Italy; EClinical Genetics and Metabolic Diseases Unit, Children Hospital Giovanni XXIII, Bari, Italy; FDepartment of Pediatrics, University of Messina, Messina, Italy; GDepartment of Pediatrics, University of Modena and Reggio Emilia, Modena, Italy


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.

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