Ann Pediatr Endocrinol Metab.  2015 Jun;20(2):110-113. 10.6065/apem.2015.20.2.110.

Turner syndrome presented with tall stature due to overdosage of the SHOX gene

• Seo GH
• Kang E
• Cho JH
• Lee BH
• Choi JH
• Kim GH
• Seo EJ
• Yoo HW

• KMID: 2368996
• DOI: http://doi.org/10.6065/apem.2015.20.2.110

Abstract

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.

Keyword

Turner syndrome; SHOX protein; Gonadal dysgenesis

MeSH Terms

Amenorrhea
Chromosome Deletion
Chromosome Disorders
Estrogen Replacement Therapy
Female
Gonadal Dysgenesis
Haploinsufficiency
Humans
Hypogonadism
Karyotype
Multiplex Polymerase Chain Reaction
Trisomy
Turner Syndrome*
X Chromosome

Figure

• 

  Fig. 1 Chromosome analysis revealed 46,X, psu idic(Xq21.2). The arrow indicates a breakpoint at Xq21.2, indicating the deletion of the Xq21.2-Xqter and duplication of the Xpter-Xq21.2.

• 

  Fig. 2 Multiple ligation-dependent probe amplification (MLPA) analysis was performed using a SALSA MLPA P018-D1 Reference Kit (MRC Holland, Amsterdam, the Netherlands) according to the manufacturer's instructions. Amplified products were separated by electrophoresis and analyzed using an ABI3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). The peak height of each probe was analyzed using Gene Mapper Software (Applied Biosystems). Duplication was detected at the Xp22.3-Xp22.2 region, including the SHOX gene.

Reference

1. Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab. 2006; 91:3897–3902. PMID: 16849410.

2. Sybert VP, McCauley E. Turner's syndrome. N Engl J Med. 2004; 351:1227–1238. PMID: 15371580.

3. Ogata T, Matsuo N. Sex chromosome aberrations and stature: deduction of the principal factors involved in the determination of adult height. Hum Genet. 1993; 91:551–562. PMID: 8340109.

4. Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet. 1997; 16:54–63. PMID: 9140395.

5. Ellison JW, Wardak Z, Young MF, Gehron Robey P, Laig-Webster M, Chiong W. PHOG, a candidate gene for involvement in the short stature of Turner syndrome. Hum Mol Genet. 1997; 6:1341–1347. PMID: 9259282.

6. Clement-Jones M, Schiller S, Rao E, Blaschke RJ, Zuniga A, Zeller R, et al. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet. 2000; 9:695–702. PMID: 10749976.

7. Oliveira CS, Alves C. The role of the SHOX gene in the pathophysiology of Turner syndrome. Endocrinol Nutr. 2011; 58:433–442. PMID: 21925981.

8. Nakamura Y, Suehiro Y, Sugino N, Sasaki K, Kato H. A case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis. Fertil Steril. 2001; 75:1224–1225. PMID: 11384655.

9. Ogata T, Kosho T, Wakui K, Fukushima Y, Yoshimoto M, Miharu N. Short stature homeobox-containing gene duplication on the der(X) chromosome in a female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature. J Clin Endocrinol Metab. 2000; 85:2927–2930. PMID: 10946905.

10. Ogata T, Inokuchi M, Ogawa M. Growth pattern and body proportion in a female with short stature homeobox-containing gene overdosage and gonadal estrogen deficiency. Eur J Endocrinol. 2002; 147:249–254. PMID: 12153748.

11. Nishi MY, Correa RV, Costa EM, Billerbeck AE, Cruzes AL, Domenice S, et al. Tall stature and poor breast development after estrogen replacement in a hypergonadotrophic hypogonadic patient with a 45,X/46,X,der(X) karyotype with SHOX gene overdosage. Arq Bras Endocrinol Metabol. 2008; 52:1282–1287. PMID: 19169482.

12. Kosho T, Muroya K, Nagai T, Fujimoto M, Yokoya S, Sakamoto H, et al. Skeletal features and growth patterns in 14 patients with haploinsufficiency of SHOX: implications for the development of Turner syndrome. J Clin Endocrinol Metab. 1999; 84:4613–4621. PMID: 10599728.

13. Ogata T, Matsuo N, Nishimura G. SHOX haploinsufficiency and overdosage: impact of gonadal function status. J Med Genet. 2001; 38:1–6. PMID: 11134233.