SHOX point mutations and deletions in Leri-Weill dyschondrosteosis

Falcinelli, Cristina; Calabrese, Giuseppe; Chiarelli, F; Cisternino, Mariangela; Sanctis, Luisa De; Pucarelli, Ida; Radetti, Giorgio; Waśniewska, Małgorzata; Weber, Giovanna; Stuppia, Liborio; Bernasconi, Sergio; Forabosco, Antonino

doi:10.1136/jmg.39.6.e33

Cited by 28 publications

(23 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Anomalies of the SHOX gene/region were present in 68% of dyschondrosteosis cases, which is similar to previous studies [8][9][10][11] and in 15% of ISS individuals. The high frequency of SHOX anomalies in the ISS group is probably the result of a bias.…”

Section: Discussionsupporting

confidence: 90%

High incidence of SHOX anomalies in individuals with short stature

Huber

Rosilio²,

Münnich³

et al. 2006

Journal of Medical Genetics

123

127

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 90%

High incidence of SHOX anomalies in individuals with short stature

Huber

Rosilio²,

Münnich³

et al. 2006

Journal of Medical Genetics

123

127

View full text Add to dashboard Cite

“…Heterozygous defects in SHOX have been identified in 56-100% of LWD cases. [7][8][9][10][11] The genotype-phenotype correlation is weak and incomplete expression in families with LWD has been demonstrated, with some patients who carry SHOX mutations presenting only short stature without the Madelung deformity. 9 Therefore, some patients who carry SHOX defects can be classified as having idiopathic short stature (ISS).…”

Section: Introductionmentioning

confidence: 99%

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

Jorge

Souza

Nishi

et al. 2006

Clinical Endocrinology

108

View full text Add to dashboard Cite

show abstract

“…[4][5][6] Mutations in the SHOX gene are one of the more frequent genetic causes of short stature in individuals with isolated or familial short stature. [7][8][9][10][11] Significant evidence points to an important role for SHOX as a mediator of linear growth. First, the gene is expressed in the developing skeleton during fetal life 6 and is specifically expressed in bone marrow fibroblasts and proliferating and hypertrophic chondrocytes 3-5 12 13 ; second, deficiency of SHOX at the growth plate is associated with marked disorganisation of chondrocyte proliferation 14 ; and third, there is a dosedependent association between the number of active copies of the SHOX gene and height, such that SHOX haploinsufficiency is associated with short stature, whereas SHOX overdose as seen in sex-chromosome polyploidy is associated with tall stature.…”

mentioning

confidence: 99%

Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency

Rappold

Blum

Shavrikova³

et al. 2007

Journal of Medical Genetics

234

248

View full text Add to dashboard Cite

Background: Short stature affects approximately 2% of children, representing one of the more frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions of the short stature homeobox-containing gene (SHOX) are found quite frequently in subjects with short stature. Haploinsufficiency of the SHOX gene causes short stature with highly variable clinical severity, ranging from isolated short stature without dysmorphic features to Léri-Weill syndrome, and with no functional copy of the SHOX gene, Langer syndrome. Methods: To characterise the clinical and molecular spectrum of SHOX deficiency in childhood we assessed the association between genotype and phenotype in a large cohort of children of short stature from 14 countries. Results: Screening of 1608 unrelated individuals with sporadic or familial short stature revealed SHOX mutations or deletions in 68 individuals (4.2%): complete deletions in 48 (70.6%), partial deletions in 4 (5.9%) and point mutations in 16 individuals (23.5%). Although mean height standard deviation score (SDS) was not different between participants of short stature with or without identified SHOX gene defects (-2.6 vs -2.6), detailed examination revealed that certain bone deformities and dysmorphic signs, such as short forearm and lower leg, cubitus valgus, Madelung deformity, high-arched palate and muscular hypertrophy, differed markedly between participants with or without SHOX gene defects (p,0.001). Phenotypic data were also compared for 33 children with Turner syndrome in whom haploinsufficiency of SHOX is thought to be responsible for the height deficit. Conclusion: A phenotype scoring system was developed that could assist in identifying the most appropriate subjects for SHOX testing. This study offers a detailed genotype-phenotype analysis in a large cohort of children of short stature, and provides quantitative clinical guidelines for testing of the SHOX gene.

show abstract

SHOX point mutations and deletions in Leri-Weill dyschondrosteosis

Cited by 28 publications

References 12 publications

High incidence of SHOX anomalies in individuals with short stature

High incidence of SHOX anomalies in individuals with short stature

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

Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency

Contact Info

Product

Resources

About