SHOX gene and conserved noncoding element deletions/duplications in Colombian patients with idiopathic short stature

Q4Artículo original95-102SHOX gene mutations or haploinsufficiency cause a wide range of phenotypes such as Leri Weill dyschondrosteosis (LWD), Turner syndrome, and disproportionate short stature (DSS). However, this gene has also been found to be mutated in cases of idiopathic short stature (ISS) with a 3–15% frequency. In this study, the multiplex ligation‐dependent probe amplification (MLPA) technique was employed to determine the frequency of SHOX gene mutations and their conserved noncoding elements (CNE) in Colombian patients with ISS. Patients were referred from different centers around the county. From a sample of 62 patients, 8.1% deletions and insertions in the intragenic regions and in the CNE were found. This result is similar to others published in other countries. Moreover, an isolated case of CNE 9 duplication and a new intron 6b deletion in another patient, associated with ISS, are described. This is one of the first studies of a Latin American population in which deletions/duplications of the SHOX gene and its CNE are examined in patients with ISS

Caracterización molecular del gen shox y sus regiones reguladoras en una muestra de pacientes con talla baja idiopática de la ciudad de Bogotá

La talla baja es un concepto para el cual se han descrito tanto variantes normales como variantes patogénicas. Una de las variantes que hace parte de la clasificación de variantes normales es la Talla baja idiopática (ISS), debido a que estos pacientes no cursan con ninguna anormalidad fenotípica y sus niveles de GH son normales. Mutaciones en el SHOX, generan un amplio espectro de fenotipos cuando hay haploinsuficiencia del gen, desde la discondrosteosis de Leri Weill (LWD), el Síndrome de Turner y la talla baja desproporcionada (DSS), sin embargo, también se ha encontrado mutado en una alta frecuencia en pacientes con ISS (cerca del 3 al 15% de la población de ISS). En este estudio se empleo la técnica MLPA para determinar la frecuencia de mutaciones en el gen shox y sus CNE en pacientes colombianos con ISS, encontrando una frecuencia del 9,6% entre deleciones e inserciones, reportando un caso aislado de una duplicación en el CNE 9 en un paciente con fenotipo de talla baja idiopática y una deleción no referenciada en el intron 6b en otro paciente con ISS. / Abstract. Short stature is a concept for which variants have been described both normal and pathogenic variants; a variant that is part of the classification of normal variants is idiopathic short stature (ISS), because these patients do not present with any phenotypic abnormalities and GH levels are normal. Shox mutations generate a wide spectrum of phenotypes when there is haploinsufficiency of the gene, since Leri Weill dischondrosteosis (LWD), Turner Syndrome and disproportionate short stature (DSS), however, has been found a high frequency of mutations in patients with ISS (about 3 to 15% of population of ISS). In this study, the MLPA technique was employed to determinate the frequency of mutations in the Shox gene and CNE in colombian patients with ISS and found a frequency of 9.6% between deletions and insertions, reporting a single case of aduplication in the CNE 9 in a patient with phenotype of ISS and one unreferenced deletion in the intron 6b in another patient with ISS.Maestrí