Short stature is a common growth disorder in childhood. It is defined as a body height which is two standard deviations (SD) or more below the mean for children of that sex, age and population. It occurs in some endocrine disorders, chronic systemic diseases, metabolic, skeletal and genetic disorders. However, a large part of the cases remains unexplained and is referred to as idiopathic short stature. One of the leading genetic causes of short stature are variants in the regulatory and coding regions of the short stature homeobox-containing gene (SHOX gene). These variants, according to references, are considered to be responsible for 2-15% of cases of idiopathic short stature. SHOX gene is located in the pseudoautosomal region of the short-arm tips of both X and Y chromosomes and is essential for the development of the skeleton. The most common SHOX defects are various deletions, which include the gene itself or its regulatory regions. Less common are duplications, nonsense and missense point mutations in the coding region of the gene.
The aim of this study was to detect any sequence variations in the SHOX gene among the Slovenian population of children with idiopathic short stature. Sanger sequencing was used for detection of point mutations, small deletions and insertions. Multiplex ligation-dependent probe amplification (MLPA) was used for the detection of larger copy number variations (CNV). Results obtained in this study were compared to the existing data.
84 children with idiopathic short stature were included in this study. All of them were referred to the Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases or Genetic ambulant at the University Children’s Hospital, University Medical Centre Ljubljana. The disease-causing variant in the SHOX gene was discovered only in one patient, which represents 1,2% of the cohort. According to these results, in the Slovenian population of children with idiopathic short stature SHOX deficiency is less frequent than expected considering existing data from other populations. Nevertheless, this is in concordance with a previous study in a smaller cohort of Slovenian patients with idiopathic short stature.