Screening of the SHOX/PAR1 region using MLPA and miRNA expression profiling in a group of Egyptian children with non-syndromic short stature

Abstract Background Short stature is defined as a body height below the third percentile, based on chronological age, or 2 standard deviations (SD) below the national height standard. The prevalence of short stature is around 2% of children worldwide. Several gene deficiencies have been associated with the etiology of short stature. The SHOX is an important candidate gene for short stature, as its haploinsufficiency underlies syndromic and non-syndromic short stature. Partial and complete duplications of SHOX have been reported in patients with short stature. Proper genetic diagnosis of these children allows for appropriate therapeutic approaches to be administered. Since copy number variation (CNV) is a possible mechanism of interhuman variability and pathogenic disease, the multiplex ligation-dependent probe amplification technique (MLPA) can be used as an initial screening technique. Cartilage tissue expresses specific microRNAs (miRNAs), which play an essential role in the regulation of chondrocyte proliferation and differentiation during growth plate development. We aimed to assess the SHOX/PAR1 region using CNV profiling for non-syndromic short stature in Egyptian children with and without growth hormone deficiency using the MLPA technique and expression profiling of miR-1, miR-15a, and miR-140 using quantitative real-time polymerase chain reaction (qRT-PCR) in a group of Egyptian children with non-syndromic short stature. Results Of the fifty cases included in this study, different CNVs were detected in ten children (20%), in/outside the SHOX region. Moreover, in children with short stature, the expression level of miRNA-140 was significantly different from that of healthy controls. Conclusions This is one of the first studies that have assessed CNVs in the SHOX/PAR1 region in a group of Egyptian children with short stature. MLPA analysis of SHOX/PAR1 identified different CNVs in children with non-syndromic short stature, suggesting that the MLPA should be used as an initial screening technique in short children, as proper genetic diagnosis of these children leads to implementation of the appropriate therapeutic approach. Alterations in the levels of miRNA-140 in children with short stature suggest that changes in the expression levels of this miRNA are associated with the pathogenesis of short stature.