SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and Léri–Weill dyschondrosteosis

Hirschfeldova, Katerina; Šolc, Roman; Baxová, A; Zapletalová, Jiřina; Kebrdlova, Vera; Gaillyová, Renata; Prášilová, Šárka; Šoukalová, Jana; Mihalová, Romana; Lněnička, Petr; Florianová, Martina; Stěkrová, J

doi:10.1016/j.gene.2011.10.011

Cited by 43 publications

(31 citation statements)

References 26 publications

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“…In addition, SHOX defects were found in 19% of the children who were originally labeled as ISS, in spite of body disproportion. These observations support previous recommendations to test for SHOX defects in children with abnormal body proportions [10,11,12,13,14,15]. …”

Section: Discussionsupporting

confidence: 90%

“…LWD is a skeletal dysplasia affecting both sexes and is characterized by short stature, mesomelia and Madelung deformity. In addition, several groups have shown that in children who were first considered as having idiopathic short stature (ISS, MIM 300582), SHOX defects can be found in 1-16% and that the assessment of body proportions may be an important selection criterion for genetic testing [10,11,12,13,14,15]. SHOX haploinsufficiency is transmitted with a pseudoautosomal dominant inheritance pattern.…”

Section: Introductionmentioning

confidence: 99%

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The Sitting Height/Height Ratio for Age in Healthy and Short Individuals and Its Potential Role in Selecting Short Children for SHOX Analysis

et al. 2013

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Aims: To determine the presence of abnormal body proportion, assessed by sitting height/height ratio for age and sex (SH/H SDS) in healthy and short individuals, and to estimate its role in selecting short children for SHOX analysis. Methods: Height, sitting height and weight were evaluated in 1,771 healthy children, 128 children with idiopathic short stature (ISS), 58 individuals with SHOX defects (SHOX-D) and 193 females with Turner syndrome (TS). Results: The frequency of abnormal body proportion, defined as SH/H SDS >2, in ISS children was 16.4% (95% CI 10-22%), which was higher than in controls (1.4%, 95% CI 0.8-1.9%, p < 0.001). The SHOX gene was evaluated in all disproportionate ISS children and defects in this gene were observed in 19%. Among patients with SHOX-D, 88% of children (95% CI 75-100%) and 96% of adults had body disproportion. In contrast, SH/H SDS >2 were less common in children (48%, 95% CI 37-59%) and in adults (28%, 95% CI 20-36%) with TS. Conclusion: Abnormal body proportions were observed in almost all individuals with SHOX-D, 50% of females with TS and 16% of children considered ISS. Defects in SHOX gene were identified in 19% of ISS children with SH/H SDS >2, suggesting that SH/H SDS is a useful tool to select children for undergoing SHOX molecular studies.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The Sitting Height/Height Ratio for Age in Healthy and Short Individuals and Its Potential Role in Selecting Short Children for SHOX Analysis

et al. 2013

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“…In humans, mutations of Shox gene function have been associated with a series of short-stature conditions, such as Léri-Weill dyschondrosteosis, Turner syndrome, and Langer dysplasia, which exhibit abnormalities in the skeletal development [22,23]. Shox2 expression has also been found in the development of limbs in a complementary pattern to that of Shox [21].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Shox2 Leads to Congenital Dysplasia of the Temporomandibular Joint in Mice

Liang

et al. 2014

IJMS

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Our previous study reported that inactivation of Shox2 led to dysplasia and ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with human Shox partially rescued the phenotype with a prematurely worn out articular disc. However, the mechanisms of Shox2 activity in TMJ development remain to be elucidated. In this study, we investigated the molecular and cellular basis for the congenital dysplasia of TMJ in Wnt1-Cre; pMes-stop Shox2 mice. We found that condyle and glenoid fossa dysplasia occurs primarily in the second week after the birth. The dysplastic TMJ of Wnt1-Cre; pMes-stop Shox2 mice exhibits a loss of Collagen type I, Collagen type II, Ihh and Gli2. In situ zymography and immunohistochemistry further demonstrate an up-regulation of matrix metalloproteinases (MMPs), MMP9 and MMP13, accompanied by a significantly increased cell apoptosis. In addition, the cell proliferation and expressions of Sox9, Runx2 and Ihh are no different in the embryonic TMJ between the wild type and mutant mice. Our results show that overexpression of Shox2 leads to the loss of extracellular matrix and the increase of cell apoptosis in TMJ dysplasia by up-regulating MMPs and down-regulating the Ihh signaling pathway.

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“…their phenotypic characteristics (short stature and dysmorphic signs) and/or family history (20,22). The clinical description of the study group is summarized in Table 1.…”

Section: Patients With Isolated Shox-dmentioning

confidence: 99%

Prepubertal Girls With Turner Syndrome and Children With Isolated SHOX Deficiency Have Similar Bone Geometry at the Radius

Souček¹,

Zapletalová

Zemková³

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:The low bone mineral density (BMD) and alterations in bone geometry observed in patients with Turner syndrome (TS) are likely caused by hypergonadotropic hypogonadism and/or by haploinsufficiency of the SHOX gene. Objective:Our objective was to compare BMD, bone geometry, and strength at the radius between prepubertal girls with TS and children with isolated SHOX deficiency (SHOX-D) to test the hypothesis that the TS radial bone phenotype may be caused by SHOX-D. Design and Setting:This comparative cross-sectional study was performed between March 2008 and May 2011 in 5 large centers for pediatric endocrinology.Patients: Twenty-two girls with TS (mean age 10.3 years) and 10 children with SHOX-D (mean age 10.3 years) were assessed using peripheral quantitative computed tomography of the forearm.Main outcomes: BMD, bone geometry, and strength at 4% and 65% sites of the radius were evaluated.Results: Trabecular BMD was normal in TS (mean Z-score ϭ Ϫ0.2 Ϯ 1.1, P ϭ .5) as well as SHOX-D patients (mean Z-score ϭ 0.5 Ϯ 1.5, P ϭ .3). At the proximal radius, we observed increased total bone area (Z-scores ϭ 0.9 Ϯ 1.5, P ϭ .013, and 1.5 Ϯ 1.4, P ϭ .001, for TS and SHOX-D patients, respectively) and thin cortex (Z-scores ϭ Ϫ0.7 Ϯ 1.2, P ϭ 0.013, and Ϫ2.0 Ϯ 1.2, P Ͻ .001, respectively) in both groups. Bone strength index was normal in TS as well as SHOX-D patients (Z-scores ϭ 0.3 Ϯ 1.0, P ϭ .2, and 0.1 Ϯ 1.3, P ϭ .8, respectively). Conclusions:The similar bone geometry changes of the radius in TS and SHOX-D patients support the hypothesis that loss of 1 copy of SHOX is responsible for the radial bone phenotype associated with TS. (J Clin Endocrinol Metab 98: E1241-E1247, 2013)

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SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and Léri–Weill dyschondrosteosis

Cited by 43 publications

References 26 publications

The Sitting Height/Height Ratio for Age in Healthy and Short Individuals and Its Potential Role in Selecting Short Children for <b><i>SHOX</i></b> Analysis

The Sitting Height/Height Ratio for Age in Healthy and Short Individuals and Its Potential Role in Selecting Short Children for <b><i>SHOX</i></b> Analysis

Overexpression of Shox2 Leads to Congenital Dysplasia of the Temporomandibular Joint in Mice

Prepubertal Girls With Turner Syndrome and Children With Isolated SHOX Deficiency Have Similar Bone Geometry at the Radius

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