RESEARCH Open Access
Screening of the SHOX/PAR1 region using
MLPA and miRNA expression profiling in a
group of Egyptian children with non-
syndromic short stature
Ola M. Eid
1*
, Maha M. Eid
1
, Amany H. Abdelrahman
2
, Rania M. A. Abdel kader
1
, Marwa Farid
1
, Rana Mahrous
1
,
Mona K. Mekkawy
1
, Alaa K. Kamel
1
, Inas Mazen
3
and Hala T. El-Bassyouni
3
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.
Keywords: Short stature, Copy number variations (CNVs), Multiplex ligation-dependent probe amplification (MLPA),
SHOX, ASMT, miRNA, miR-140
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* Correspondence: olameid@hotmail.com
1
Department of Human Cytogenetics, Human Genetics and Genome
Research Division, National Research Centre, El Bohouth Street, 12311, Dokki,
Cairo, Egypt
Full list of author information is available at the end of the article
Egyptian Journal of Medical
Human Genetics
Eid et al. Egyptian Journal of Medical Human Genetics (2020) 21:47
https://doi.org/10.1186/s43042-020-00090-4