The role of the SHOX gene in the pathophysiology of Turner syndrome

Oliveira, Conceição Silva; Alves, Crésio

doi:10.1016/j.endonu.2011.06.005

Cited by 39 publications

(31 citation statements)

References 50 publications

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“…Short stature homeobox-containing gene, or SHOX , is located at pseudoautosomal region 1 (PAR1) of Xp22.33 and Yp11.2 [ 16 - 18 ]. SHOX protein is a transcriptional factor for chondrocyte differentiation.…”

Section: Genetic Causes Of Issmentioning

confidence: 99%

Novel genetic cause of idiopathic short stature

Kang

2017

Ann Pediatr Endocrinol Metab

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Traditionally, the growth hormone – insulin-like growth factor I (GH – IGF-I) axis is the most important signaling pathway in linear growth, and defects in this axis present as growth hormone deficiencies or IGF-I deficiencies. However, subtle changes in serum levels of GH or IGF-I, caused by gene mutations involved in the GH – IGF-I axis, can present as idiopathic short stature (ISS). This paper briefly discusses GHR and IGFALS. In addition, recent studies have shown that many factors, including paracrine signals, extracellular matrix, and intracellular mechanisms of chondrocytes, regulate the growth plate independent of the GH – IGF-I system. Rapid development of diagnostic technologies has enabled discovery of many genetic causes of ISS. This paper discusses 5 genes, SHOX, NPR2, NPPC, FGFR3, and ACAN, that may lead to better understanding of ISS.

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Section: Genetic Causes Of Issmentioning

confidence: 99%

Novel genetic cause of idiopathic short stature

Kang

2017

Ann Pediatr Endocrinol Metab

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“…Turner syndrome (TS) is one of the most common sex chromosome abnormalities 108,109 and results from the complete or partial loss of the X chromosome. Most individuals with TS have short stature, which is associated with the loss of the SHOX gene [110][111][112] . These individuals are at increased risk for neurodevelopmental issues, including learning disabilities, visuo-spatial, social and executive function impairments 113 and epilepsy [114][115][116][117][118] .…”

Section: Discussionmentioning

confidence: 99%

The transcription factor Shox2 shapes thalamocortical neuron firing and synaptic properties

Maroteaux

Song

et al. 2019

Preprint

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Thalamocortical neurons (TCNs) transmit information about sensory stimuli from the thalamus to the cortex. In response to different physiological states and demands TCNs can fire in tonic and/or phasic burst modes. These firing properties of TCNs are supported by precisely timed inhibitory synaptic inputs from the thalamic reticular nucleus and intrinsic currents, including T-type Ca 2+ and HCN currents. These intrinsic currents are mediated by Cav3.1 and HCN channel subunits, and alterations in expression or modulation of these channels can have dramatic implications on thalamus function. The factors that regulate these currents controlling the firing patterns important for integration of the sensory stimuli and the consequences resulting from the disruption of these firing patterns are not well understood. Shox2 is a transcription factor known to be important for pacemaker activity in the heart. We show here that Shox2 is also expressed in adult mouse thalamus. We hypothesized that genes regulated by Shox2's transcriptional activity may be important for physiological properties of TCNs. In this study, we used RNA sequencing on control and Shox2 knockout mice to determine Shox2-affected genes and revealed a network of ion channel genes important for neuronal firing properties. Quantitative PCR confirmed that expression of Hcn2, 4 and Cav3.1 genes were affected by Shox2 KO. Western blotting showed expression of the proteins for these channels was decreased in the thalamus, and electrophysiological recordings showed that Shox2 KO impacted the firing and synaptic properties of TCNs. Finally, behavioral studies revealed that Shox2 expression in TCNs play a role in somatosensory function and object recognition memory. Overall, these results reveal Shox2 as a transcription factor important for TCN firing properties and thalamic function. 1 Processing of sensory information is mediated by precise circuitry that senses stimuli in 2 the periphery and transforms the information through a network of synaptic connections to 3 ultimately allow perception and cognitive processing of the surrounding world. Rhythmic 4 oscillations of brain activity crucial to cognitive function emerge from neuronal network 5 interactions that consist of reciprocal connections between the thalamus, the inhibitory 6 thalamic reticular nucleus and the cortex 1 . Dysfunction of these oscillations caused by 7 aberrant activity in the thalamic circuit is thought to play a role in many neuropathological 8 conditions, including epilepsy 2-4 , autism 5-7 , and schizophrenia [8][9][10][11] . Furthermore, damage to 9 thalamic nuclei, especially medial and anterior nuclei, causes severe memory deficits known 10 as diencephalic amnesia 12-17 . 11 The intrinsic properties that shape action potential firing and contribute to rhythmic 12 oscillations of the thalamocortical neurons (TCNs) are important for efficient transfer of 13 information from the thalamus to the cortex. Notably, TCNs switch their firing states between 14 2 modes, burst and tonic fi...

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“…This gene was discovered on the distal part of PAR1, and was designated the short stature homeobox-containing ( SHOX ) gene or pseudoautosomal homeobox-containing osteogenic ( PHOG ) gene 4 5) . The SHOX gene is expressed in limbs, pharyngeal arches, osteogenic cells, and bone marrow fibroblasts, and is involved in skeletal growth and development 6 7) . The loss of the SHOX gene therefore leads to short stature and various skeletal abnormalities, such as short metacarpals, high-arched palate, cubitus valgus, Madelung deformity, and mesomelia 6 7) .…”

Section: Introductionmentioning

confidence: 99%

“…The SHOX gene is expressed in limbs, pharyngeal arches, osteogenic cells, and bone marrow fibroblasts, and is involved in skeletal growth and development 6 7) . The loss of the SHOX gene therefore leads to short stature and various skeletal abnormalities, such as short metacarpals, high-arched palate, cubitus valgus, Madelung deformity, and mesomelia 6 7) . The SHOX gene is expressed on both the inactive X chromosome and the active X or Y chromosome, thereby escaping from X chromosome inactivation 4) .…”

Section: Introductionmentioning

confidence: 99%

Turner syndrome presented with tall stature due to overdosage of theSHOXgene

Seo

Kang

Cho

et al. 2015

Ann Pediatr Endocrinol Metab

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Turner syndrome is one of the most common chromosomal disorders. It is caused by numerical or structural abnormalities of the X chromosome and results in short stature and gonadal dysgenesis. The short stature arises from haploinsufficiency of the SHOX gene, whereas overdosage contributes to tall stature. This report describes the first Korean case of Turner syndrome with tall stature caused by SHOX overdosage. The patient presented with primary amenorrhea and hypergonadotropic hypogonadism at the age of 17 years. Estrogen replacement therapy was initiated at that time. She displayed tall stature from childhood, with normal growth velocity, and reached a final height of 190 cm (standard deviation score, 4.3) at the age of 30 years. Her karyotype was 46,X, psu idic(X)(q21.2), representing partial monosomy of Xq and partial trisomy of Xp. Analysis by multiplex ligation-dependent probe amplification detected a duplication at Xp22.3-Xp22.2, encompassing the PPP2R3 gene near the 5'-end of the SHOX gene through the FANCD gene at Xp22.2.

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The role of the SHOX gene in the pathophysiology of Turner syndrome

Cited by 39 publications

References 50 publications

Novel genetic cause of idiopathic short stature

Novel genetic cause of idiopathic short stature

The transcription factor Shox2 shapes thalamocortical neuron firing and synaptic properties

Turner syndrome presented with tall stature due to overdosage of theSHOXgene

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