Enhancer Elements Upstream of the SHOX Gene Are Active in the Developing Limb

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2009 Dec 10

PMID 19997128

Citations 21

Authors

Claudia Durand

Fiona Bangs

Jason Signolet

Eva Decker

Cheryll Tickle

Gudrun Rappold

Affiliations

Soon will be listed here.

Abstract

Léri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.

Citing Articles

RARE DOSAGE ABNORMALITIES - COPY NUMBER VARIATIONS FLANKING THE SHOX GENE.

Gherlan I, Braha E, Manole D, Radomir L, Nedelcu I, Popa O Acta Endocrinol (Buchar). 2023; 19(1):115-124.

PMID: 37601716 PMC: 10439321. DOI: 10.4183/aeb.2023.115.

Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri-Weill dyschondrosteosis.

Fanelli A, Vannelli S, Babu D, Mellone S, Cucci A, Monzani A Mol Genet Genomic Med. 2021; 10(1):e1793.

PMID: 34811950 PMC: 8801136. DOI: 10.1002/mgg3.1793.

SHOX CNE9/10 Knockout in U2OS Osteosarcoma Cells and Its Effects on Cell Growth and Apoptosis.

Xu X, Xin S, Mao H, Zhang H, Chen L, Li L Med Sci Monit. 2020; 26:e921233.

PMID: 32032347 PMC: 7020756. DOI: 10.12659/MSM.921233.

Safety Outcomes and Near-Adult Height Gain of Growth Hormone-Treated Children with SHOX Deficiency: Data from an Observational Study and a Clinical Trial.

Benabbad I, Rosilio M, Child C, Carel J, Ross J, Deal C Horm Res Paediatr. 2016; 87(1):42-50.

PMID: 28002818 PMC: 5348728. DOI: 10.1159/000452973.

Detection of SHOX gene aberrations in routine diagnostic practice and evaluation of phenotype scoring form effectiveness.

Hirschfeldova K, Florianova M, Kebrdlova V, Urbanova M, Stekrova J J Hum Genet. 2016; 62(2):253-257.

PMID: 27708272 DOI: 10.1038/jhg.2016.117.

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