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. 2017 Oct;60(10):327-332.
doi: 10.3345/kjp.2017.60.10.327. Epub 2017 Oct 20.

Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature

Abdulla A Alharthi  1   2   3 , Ehab I El-Hallous  1   4 , Iman M Talaat  5 , Hamed A Alghamdi  2 , Matar I Almalki  6 , Ahmed Gaber  1   7
Affiliations

Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature

Abdulla A Alharthi et al. Korean J Pediatr. 2017 Oct.

Abstract

Purpose: Short stature affects approximately 2%-3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene (SHOX) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations.

Methods: We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated.

Results: A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX.

Conclusion: In Saudi Arabia ISS patients, rather than SHOX, it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

Keywords: Anthropometric measures; Idiopathic short stature; Molecular sequence; SHOX gene.

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Conflict of interest statement

Conflict of interest: No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1. Polymorphic variant detected in exon 4 in homeodomain of SHOX in Idiopathic short stature patients. Missense mutation in heterozygous genotype form c.528 G>C, p.E176D. Black arrow indicates the site of mutation.
Fig. 2
Fig. 2. Polymorphic variants detected in noncoding region exon 1 of SHOX in Idiopathic short stature (ISS) patients. (A) novel insertion variant c.-645_-646 InsTGT, (B) polymorphic variant c.-512 C>A, (C) polymorphic variant c.-507 G>C, and (D) both variants in the same ISS patients. Black arrows indicate the site of the variant.
Fig. 3
Fig. 3. Polymorphic variant detected in 5′UTR region of exon 2 of SHOX in Idiopathic short stature patients. (A) Homozygous genotype form c.-372 G>A and (B) heterozygous genotype form c.-372 G>A. Black arrows indicate the site of the variant.
Fig. 4
Fig. 4. Polymorphic variants detected in exon 6a of SHOX in idiopathic short stature patients. (A) Novel missense variant (c.*41C>A) in homozygous form (A1) and heterozygous form (A2), (B) Novel variant (c.*284_285 Ins(dup)AG). Black arrows indicate the site of the variant.
See this image and copyright information in PMC

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