Background: The short stature homeobox-containing (SHOX) gene, loeated in tbe telomeric pseudoautosomal region l (PARI) on the sfiort arm of both sex chromosomes, is important for linear growtb. SHOX defieiency is nOI only the cause of Leri-Weill dyschondrosteosis but is also involved in idiopathic short stature (ISS). Objective and hypotheses: The aim 01' this study was the assessment of SHOX deletions and mutations in ehildren wilh ISS in order to estimate the frequeney and c1arify possible genotypelphenotype eorrelations. Methods: This study, supported by tbe Eli LìIly Italia and approved by tbe ltalian Soeiety for Pediatric Endocrinology and Diabetes (lSPED), is a multicenter study inc1uding several ltalian Pediallic Endoerinology Units. We collected almost 100 blood samples from patients with ISS and various degrec of skeletal alterations. Genomic DNA was extracted and used for Multiplex Ligation-dependent Probe Amplification (MLPA) and sequencing analysis. MLPA was performed using tbe SALSA MLPA POI8-FI SHOX probe mix kit analyzing both the eoding region and the enhancer of the SHOX gene in the Pediatric Laboratory of Parma. Results: Out ofthe first 50 patients analyzed, 5 presented a big deletion oftbe SHOX gene, inc1uding tbe sister and mother of one of the probands. Other 3 patients showed an alteration ofcytokine receptor-like factor 2 (CRLF2) and arylsulfatase F (ARSF) genes, being tllese genes involved in celi proliferation and bone/cartilage eomposition, respectively. Three patients had a complex genetic asset ofchromosome X to be confirmed. No mutations wcre detected by sequencing. ConcJusions: In OUT cohort ofpatients with ISS tbc incidenee ofSHOX gene deletions is 6%, in accordance with some oftbe previous repom. Auxological measurements ofbody proportions (mesomelia), the presenee of minor skeletal abnormalities, and the search for subtle radiographic signs are important keys leading lo the appropriate indicatìon for genetic analysìs.
Incidence of SHOX deficiency in a cohort of Italian children with idiopathic short stature
WASNIEWSKA, Malgorzata Gabriela;
2013-01-01
Abstract
Background: The short stature homeobox-containing (SHOX) gene, loeated in tbe telomeric pseudoautosomal region l (PARI) on the sfiort arm of both sex chromosomes, is important for linear growtb. SHOX defieiency is nOI only the cause of Leri-Weill dyschondrosteosis but is also involved in idiopathic short stature (ISS). Objective and hypotheses: The aim 01' this study was the assessment of SHOX deletions and mutations in ehildren wilh ISS in order to estimate the frequeney and c1arify possible genotypelphenotype eorrelations. Methods: This study, supported by tbe Eli LìIly Italia and approved by tbe ltalian Soeiety for Pediatric Endocrinology and Diabetes (lSPED), is a multicenter study inc1uding several ltalian Pediallic Endoerinology Units. We collected almost 100 blood samples from patients with ISS and various degrec of skeletal alterations. Genomic DNA was extracted and used for Multiplex Ligation-dependent Probe Amplification (MLPA) and sequencing analysis. MLPA was performed using tbe SALSA MLPA POI8-FI SHOX probe mix kit analyzing both the eoding region and the enhancer of the SHOX gene in the Pediatric Laboratory of Parma. Results: Out ofthe first 50 patients analyzed, 5 presented a big deletion oftbe SHOX gene, inc1uding tbe sister and mother of one of the probands. Other 3 patients showed an alteration ofcytokine receptor-like factor 2 (CRLF2) and arylsulfatase F (ARSF) genes, being tllese genes involved in celi proliferation and bone/cartilage eomposition, respectively. Three patients had a complex genetic asset ofchromosome X to be confirmed. No mutations wcre detected by sequencing. ConcJusions: In OUT cohort ofpatients with ISS tbc incidenee ofSHOX gene deletions is 6%, in accordance with some oftbe previous repom. Auxological measurements ofbody proportions (mesomelia), the presenee of minor skeletal abnormalities, and the search for subtle radiographic signs are important keys leading lo the appropriate indicatìon for genetic analysìs.Pubblicazioni consigliate
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