A Novel TSC1 Variant Associated with Tuberous Sclerosis and Sacrococcygeal Teratoma

Overview

Journal Hum Genome Var

Date 2020 Dec 10

PMID 33298910

Authors

Saba Ahmad

Luis Manon

Gifty Bhat

Jerry Machado

Alice Zalan

Nikolas Mata-Machado

Steven Garzon

Akira Yoshii

Affiliations

Soon will be listed here.

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

References

Presneau N, Shalaby A, Idowu B, Gikas P, Cannon S, Gout I . Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway. Br J Cancer. 2009; 100(9):1406-14. PMC: 2694420. DOI: 10.1038/sj.bjc.6605019. View

Kawano H, Ito Y, Kanai F, Nakamura E, Tada N, Takai S . Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway. Oncol Rep. 2015; 34(5):2251-8. PMC: 4583534. DOI: 10.3892/or.2015.4254. View

Plank T, Yeung R, Henske E . Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Cancer Res. 1998; 58(21):4766-70. View

Kombogiorgas D, St George E, Chapman S, English M, Solanki G . Infantile clivus chordoma without clivus involvement: case report and review of the literature. Childs Nerv Syst. 2006; 22(10):1369-74. DOI: 10.1007/s00381-006-0069-8. View

Ito Y, Kawano H, Kanai F, Nakamura E, Tada N, Takai S . Establishment of Tsc2‑deficient rat embryonic stem cells. Int J Oncol. 2015; 46(5):1944-52. DOI: 10.3892/ijo.2015.2913. View

Kimura Y, Sugimura H, Toda M, Nakamura Y, Shibuya K, Murakami A . A case of 2-year-old boy with tuberous sclerosis complicated with descending aortic aneurysm. Pediatr Int. 2005; 47(2):224-6. DOI: 10.1111/j.1442-200x.2005.02031.x. View

Borgel J, Olschewski H, Reuter T, Miterski B, Epplen J . Does the tuberous sclerosis complex include clivus chordoma? A case report. Eur J Pediatr. 2001; 160(2):138. DOI: 10.1007/s004310000645. View

Kandt R, Haines J, Smith M, Northrup H, Gardner R, Short M . Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet. 1992; 2(1):37-41. DOI: 10.1038/ng0992-37. View

. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993; 75(7):1305-15. DOI: 10.1016/0092-8674(93)90618-z. View

10.

Crino P, Nathanson K, Henske E . The tuberous sclerosis complex. N Engl J Med. 2006; 355(13):1345-56. DOI: 10.1056/NEJMra055323. View

11.

van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S . Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997; 277(5327):805-8. DOI: 10.1126/science.277.5327.805. View

12.

van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A . Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. 1998; 7(6):1053-7. DOI: 10.1093/hmg/7.6.1053. View

13.

Lountzis N, Hogarty M, Kim H, Junkins-Hopkins J . Cutaneous metastatic chordoma with concomitant tuberous sclerosis. J Am Acad Dermatol. 2006; 55(2 Suppl):S6-10. DOI: 10.1016/j.jaad.2005.08.061. View

14.

Storm P, Magge S, Kazahaya K, Sutton L . Cervical chordoma in a patient with tuberous sclerosis presenting with shoulder pain. Pediatr Neurosurg. 2007; 43(2):167-9. DOI: 10.1159/000098396. View

15.

Lee-Jones L, Aligianis I, Davies P, Puga A, Farndon P, Stemmer-Rachamimov A . Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2. Genes Chromosomes Cancer. 2004; 41(1):80-5. DOI: 10.1002/gcc.20052. View

16.

Dahl N, Luebbert T, Loi M, Neuberger I, Handler M, Kleinschmidt-DeMasters B . Chordoma Occurs in Young Children With Tuberous Sclerosis. J Neuropathol Exp Neurol. 2017; 76(6):418-423. PMC: 6075544. DOI: 10.1093/jnen/nlx032. View

17.

Dutton R, Singleton E . Tuberous sclerosis: a case report with aortic aneurysm and unusual rib changes. Pediatr Radiol. 1975; 3(3):184-6. DOI: 10.1007/BF01006909. View

18.

Sarbassov D, Ali S, Sabatini D . Growing roles for the mTOR pathway. Curr Opin Cell Biol. 2005; 17(6):596-603. DOI: 10.1016/j.ceb.2005.09.009. View

19.

Nix W, Steuber C, Hawkins E, STENBACK W, Pokorny W, Fernbach D . Sacrococcygeal chordoma in a neonate with multiple anomalies. J Pediatr. 1978; 93(6):995-8. DOI: 10.1016/s0022-3476(78)81235-9. View

20.

Kimmell K, Dayoub H, Stolzenberg E, Sincoff E . Chordoma in the lateral medullary cistern in a patient with tuberous sclerosis: A case report and review of the literature. Surg Neurol Int. 2010; 1:13. PMC: 2908358. DOI: 10.4103/2152-7806.63908. View