<i>SHOX</i> mutations in idiopathic short stature and Leri‐Weill dyschondrosteosis: frequency and phenotypic variability

Jorge, Alexander A L; Souza, S. C. A. L.; Nishi, Mirian Yumie; Billerbeck, Ana Elisa C.; Libório, Débora C. C.; Kim, Chong; Arnhold, Ivo J.P.; Mendonça, Berenice Bilharinho

doi:10.1111/j.1365-2265.2006.02698.x

Cited by 95 publications

(110 citation statements)

References 30 publications

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“…It has been used as an important auxological parameter, essential in the clinical evaluation of children with growth and/or pubertal disturbances (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

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Sitting-height measures are related to body mass index and blood pressure levels in children

Marcato

Sampaio

Alves

et al. 2014

Arq Bras Endocrinol Metab

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Objective: Sitting height (SH) is an important parameter in the evaluation of children with grow th and pubertal disorders. Besides this, it has been viewed as a biomarker of cardiovascular risk, which is increased in adults with relatively short legs. So, the aim of this study was to evaluate the relationship between body proportions and cardiovascular risk markers in children. Subjects and methods: Eight hundred and seventeen children aged 6-13 years were evaluated. Weight, height, sitting-height (SH), sitting-height/height (SH/H), body mass index (BMI) and blood pressure (BP) were assessed and converted to standard deviation scores (SDS) for age and sex. Statistical analyses were performed. Results: There was a positive association of BMI SDS with SH and SH/H SDS (p < 0.001). Overweight children showed SH 0.8 SDS superior to eutrophic children (p < 0.001). SH SDS was also directly related to BP SDS, but this association was not independent of the association between obesity and BP when assessed by multiple regression analyzes. Conclusion: Measures of SH are strongly associated with BMI and BP in children, although the association between SH and BP is probably dependent on the association of both those variables with BMI. This is (an) important information for correct interpretation of SH values in children. Arq Bras Endocrinol Metab. 2014;58(8):802-6 Keywords Sitting height; obesity; hypertension; children RESUMO Objetivo: A altura sentada (sitting height, SH) é um importante parâmetro na avaliação de crianças com distúrbios do crescimento e da puberdade. Além disso, tem sido vista como um marcador de risco cardiovascular, aumentado em adultos com pernas relativamente curtas. O objetivo deste estudo foi avaliar a relação entre proporções corporais e marcadores de risco cardiovascular em crianças. Sujeitos e métodos: Oitocentas e dezessete crianças de 6 a 13 anos foram avaliadas. Peso, altura, altura sentada (SH), altura sentada/total (SH/H), índice de massa corpó-rea (IMC) e pressão arterial (PA) foram avaliados e convertidos em Z escores ajustados para sexo e idade. Análises estatísticas apropriadas foram desenvolvidas. Resultados: Houve associação positiva do Z-IMC com o SH e o SH/H (p < 0,001). Crianças com excesso de peso demonstraram Z-SH 0,8 superior ao de crianças eutróficas (p < 0,001). O Z-SH também apresentou correlação direta com o Z-PA, mas essa associação não foi independente da relação entre IMC e PA quando analisada por meio de regressão linear múltipla. Conclusão: Medidas de SH são fortemente associadas ao IMC e PA em crianças, embora a associação entre SH e PA seja provavelmente dependente da associação de ambas as variáveis com o IMC. Essa é uma importante informação para a correta interpretação dos valores de SH em crianças. Arq Bras Endocrinol Metab. 2014;58(8):802-6 Descritores Altura sentada; obesidade; hipertensão; crianças

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“…It has been used as an important auxological parameter, essential in the clinical evaluation of children with growth and/or pubertal disturbances (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…In adults, relatively long members have been associated with increased risk of cancer (2), while relatively short members have been associated to higher rates of diabetes, dyslipidemia (8,9), hypertension (9,10) and adverse cardiovascular outcomes (3,11). In children, few studies were directed to those associations.…”

Section: Introductionmentioning

confidence: 99%

Sitting-height measures are related to body mass index and blood pressure levels in children

Marcato

Sampaio

Alves

et al. 2014

Arq Bras Endocrinol Metab

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“…All the patients were diagnosed with ISS according to following criteria: 1) height below 3rd percentile or -2 SDs with normal body proportions; 2) normal growth hormone levels and normal response to growth hormone stimulation tests; 3) normal karyotype; 4) absence of congenital skeletal abnormalities or dysmorphic features; 5) absence of chronic, metabolic, and systemic diseases or nutritional problems; and 6) normal parental height (1)(2)(3)(4)8,(11)(12)(13)(14)(15). Appropriate written informed consent was obtained and study participants were screened for microdeletions and/or mutations in the SHOX gene.…”

Section: Patientsmentioning

confidence: 99%

“…Several monogenic genetic causes are known in short stature. One of these genes is the short stature homeobox-containing gene (SHOX) encoding a homeodomain transcription factor (3,4). This gene, localized on pseudoautosomal region (PAR) 1 of the X and Y chromosomes, has been specifically associated with some cases of idiopathic short stature (ISS) and the short stature of patients with Turner syndrome (4).…”

Section: Introductionmentioning

confidence: 99%

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Microdeletion and mutation analysis of the SHOX gene in patients with idiopathic short stature with FISH and sequencing

2018

Turk J Med Sci

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The aim of this study was to investigate the prevalence of the microdeletions and mutations of the SHOX gene in children with idiopathic short stature (ISS) by the usage of fluorescence in situ hybridization (FISH) and direct sequencing technique.Materials and methods: Thirty-seven children referred to our clinic because of short stature were classified as having ISS after clinical examination. Chromosome analyses, FISH analysis of the SHOX gene, and direct sequencing of the coding exons of SHOX, through the second to the sixth exon, in 24 of the 37 patients were also performed.Results: All children had normal karyotypes and the SHOX gene region was found to be intact in all. No mutation was detected in the exonic sequences and exon/intron boundaries of the SHOX gene in 24 children analyzed. Conclusion:No mutation was detected in the exonic sequences and exon/intron boundaries of the SHOX gene and this indicated that the prevalence of the SHOX mutations can differ according to the selection criteria, used methods, sample size, and population.

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Genetics of SHOX Deficiency

Funari

Nishi

Scalco

et al. 2012

Encyclopedia of Life Sciences

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Isolated heterozygous SHOX defects are the most frequent monogenic cause of short stature, being associated with several phenotypes ranging from idiopathic short stature (ISS) without any specific features to Léri–Weill dyschondrosteosis. SHOX deficiency is also accountable for some clinical findings detected in Turner syndrome. SHOX gene is highly expressed in osteogenic cells and encodes a transcription factor, which is essential for bone development and growth. Molecular analysis of SHOX is essential as it can identify the aetiology of short stature, enables early diagnosis in other family members, allows genetic counselling and also supports the use of rhGH therapy in affected children. Even 14 years after the discovery of SHOX , and countless published studies, little is known about the real function of this gene and the mechanisms underlying SHOX ‐related disorders. Further investigations will be essential for better understanding the exact role of this gene in the biological growth process. Key Concepts: Isolated SHOX gene defects are the most frequent monogenic cause of short stature. SHOX gene encodes a transcriptional activator, which is a member of the paired‐like homeodomain proteins. SHOX is predominantly expressed in osteogenic cells and is essential for bone development and growth. The loss of one active allele leads to growth deficit, resulting in a wide spectrum of short stature phenotypes, including Léri–Weill dyschondrosteosis (LWD) and idiopathic short stature (ISS) with no specific skeletal features. The molecular analysis of SHOX gene elucidates the aetiology of short stature, enables genetic counselling and supports the use of recombinant growth hormone treatment. Heterozygous SHOX mutations are identified in approximately 50–90% of patients with LWD. Approximately 2–15% of patients with ISS have SHOX defects. Deletions are responsible for approximately 80% of SHOX haploinsufficiency. Longitudinal follow‐up studies of children with SHOX defects suggest a relatively well‐preserved prepubertal growth followed by compromised pubertal growth due to premature growth plate fusion. Recombinant human growth hormone therapy improves growth velocity and final height in prepubertal patients with isolated SHOX haploinsufficiency.

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SHOX mutations in idiopathic short stature and Leri‐Weill dyschondrosteosis: frequency and phenotypic variability

Cited by 95 publications

References 30 publications

Sitting-height measures are related to body mass index and blood pressure levels in children

Sitting-height measures are related to body mass index and blood pressure levels in children

Microdeletion and mutation analysis of the SHOX gene in patients with idiopathic short stature with FISH and sequencing

Genetics of SHOX Deficiency

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