Phenotypes associated with SHOX deficiency

J. L. Ross, Jr Scott C., P. Marttila, K. Kowal, A. Nass, P. Papenhausen, J. Abboudi, L. Osterman, H. Kushner, P. Carter, M. Ezaki, F. Elder, F. Wei, H. Chen, A. R. Zinn

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Leri-Weill dyschondrosteosis (LWD) (MIM 127300) is a dominantly inherited skeletal dysplasia characterized phenotypically by Madelung wrist deformity, mesomelia, and short stature. LWD can now be defined genetically by haploinsufficiency of the SHOX (short stature homeobox-containing) gene. We have studied 21 LWD families (43 affected LWD subjects, including 32 females and 11 males, ages 3-56 yr) with confirmed SHOX abnormalities. We investigated the relationship between SHOX mutations, height deficit, and Madelung deformity to determine the contribution of SHOX haploinsufficiency to the LWD and Turner syndrome (TS) phenotypes. Also, we examined the effects of age, gender, and female puberty (estrogen) on the LWD phenotype. SHOX deletions were present in affected individuals from 17 families (81%), and point mutations were detected in 4 families (19%). In the LWD subjects, height deficits ranged from -4.6 to +0.6 SD (mean ± SD = -2.2 ± 1.0). There were no statistically significant effects of age, gender, pubertal status, or parental origin of SHOX mutations on height z-score. The height deficit in LWD is approximately two thirds that of TS. Madelung deformity was present in 74% of LWD children and adults and was more frequent and severe in females than males. The prevalence of the Madelung deformity was higher in the LWD vs. a TS population. The prevalence of increased carrying angle, high arched palate, and scoliosis was similar in the two populations. In conclusion, SHOX deletions or mutations accounted for all of our LWD cases. SHOX haploinsufficiency accounts for most, but not all, of the TS height deficit. The LWD phenotype shows some gender- and age-related differences.

Original languageEnglish (US)
Pages (from-to)5674-5680
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number12
DOIs
StatePublished - 2001

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Homeobox Genes
Estrogens
Genes
Phenotype
Turner Syndrome
Haploinsufficiency
Leri-Weil syndrome
Mutation
Palate
Sequence Deletion
Scoliosis
Puberty
Wrist
Point Mutation
Population

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Ross, J. L., Scott C., J., Marttila, P., Kowal, K., Nass, A., Papenhausen, P., ... Zinn, A. R. (2001). Phenotypes associated with SHOX deficiency. Journal of Clinical Endocrinology and Metabolism, 86(12), 5674-5680. https://doi.org/10.1210/jc.86.12.5674

Phenotypes associated with SHOX deficiency. / Ross, J. L.; Scott C., Jr; Marttila, P.; Kowal, K.; Nass, A.; Papenhausen, P.; Abboudi, J.; Osterman, L.; Kushner, H.; Carter, P.; Ezaki, M.; Elder, F.; Wei, F.; Chen, H.; Zinn, A. R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 12, 2001, p. 5674-5680.

Research output: Contribution to journalArticle

Ross, JL, Scott C., J, Marttila, P, Kowal, K, Nass, A, Papenhausen, P, Abboudi, J, Osterman, L, Kushner, H, Carter, P, Ezaki, M, Elder, F, Wei, F, Chen, H & Zinn, AR 2001, 'Phenotypes associated with SHOX deficiency', Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 12, pp. 5674-5680. https://doi.org/10.1210/jc.86.12.5674
Ross JL, Scott C. J, Marttila P, Kowal K, Nass A, Papenhausen P et al. Phenotypes associated with SHOX deficiency. Journal of Clinical Endocrinology and Metabolism. 2001;86(12):5674-5680. https://doi.org/10.1210/jc.86.12.5674
Ross, J. L. ; Scott C., Jr ; Marttila, P. ; Kowal, K. ; Nass, A. ; Papenhausen, P. ; Abboudi, J. ; Osterman, L. ; Kushner, H. ; Carter, P. ; Ezaki, M. ; Elder, F. ; Wei, F. ; Chen, H. ; Zinn, A. R. / Phenotypes associated with SHOX deficiency. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 12. pp. 5674-5680.
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abstract = "Leri-Weill dyschondrosteosis (LWD) (MIM 127300) is a dominantly inherited skeletal dysplasia characterized phenotypically by Madelung wrist deformity, mesomelia, and short stature. LWD can now be defined genetically by haploinsufficiency of the SHOX (short stature homeobox-containing) gene. We have studied 21 LWD families (43 affected LWD subjects, including 32 females and 11 males, ages 3-56 yr) with confirmed SHOX abnormalities. We investigated the relationship between SHOX mutations, height deficit, and Madelung deformity to determine the contribution of SHOX haploinsufficiency to the LWD and Turner syndrome (TS) phenotypes. Also, we examined the effects of age, gender, and female puberty (estrogen) on the LWD phenotype. SHOX deletions were present in affected individuals from 17 families (81{\%}), and point mutations were detected in 4 families (19{\%}). In the LWD subjects, height deficits ranged from -4.6 to +0.6 SD (mean ± SD = -2.2 ± 1.0). There were no statistically significant effects of age, gender, pubertal status, or parental origin of SHOX mutations on height z-score. The height deficit in LWD is approximately two thirds that of TS. Madelung deformity was present in 74{\%} of LWD children and adults and was more frequent and severe in females than males. The prevalence of the Madelung deformity was higher in the LWD vs. a TS population. The prevalence of increased carrying angle, high arched palate, and scoliosis was similar in the two populations. In conclusion, SHOX deletions or mutations accounted for all of our LWD cases. SHOX haploinsufficiency accounts for most, but not all, of the TS height deficit. The LWD phenotype shows some gender- and age-related differences.",
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AU - Ross, J. L.

AU - Scott C., Jr

AU - Marttila, P.

AU - Kowal, K.

AU - Nass, A.

AU - Papenhausen, P.

AU - Abboudi, J.

AU - Osterman, L.

AU - Kushner, H.

AU - Carter, P.

AU - Ezaki, M.

AU - Elder, F.

AU - Wei, F.

AU - Chen, H.

AU - Zinn, A. R.

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