Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma

Patrick R. Blackburn, Oscar F. Chacon-Camacho, Xilma R. Ortiz-González, Mariana Reyes, Graciela A. Lopez-Uriarte, Shabnam Zarei, Elizabeth J. Bhoj, Sofia Perez-Solorzano, Rachael A. Vaubel, Marine I. Murphree, Jessica Nava, Vianney Cortes-Gonzalez, Joseph E Parisi, Cristina Villanueva-Mendoza, Iris G. Tirado-Torres, Dong Li, Eric W Klee, Pavel N. Pichurin, Juan C. Zenteno

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

SOX2 is a transcription factor that is essential for maintenance of pluripotency and has several conserved roles in early embryonic development. Heterozygous loss-of-function variants in SOX2 are identified in approximately 40% of all cases of bilateral anophthalmia/micropthalmia (A/M). Increasingly SOX2 mutation-positive patients without major eye findings, but with a range of other developmental disorders including autism, mild to moderate intellectual disability with or without structural brain changes, esophageal atresia, urogenital anomalies, and endocrinopathy are being reported, suggesting that the clinical phenotype associated with SOX2 loss is much broader than previously appreciated. In this report we describe six new cases, four of which carry novel pathogenic SOX2 variants. Four cases presented with bilateral anophthalmia in addition to extraocular involvement. Another individual presented with only unilateral anophthalmia. One individual did not have any eye findings but presented with a suprasellar teratoma in infancy and was found to have the recurrent c.70del20 mutation in SOX2 (c.70_89del, p.Asn24Argfs*65). This is this first time this tumor type has been reported in the context of a de novo SOX2 mutation. Notably, individuals with hypothalamic hamartomas and slow-growing hypothalamo-pituitary tumors have been reported previously, but it is still unclear how SOX2 loss contributes to their formation.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part A
DOIs
StateAccepted/In press - Jan 1 2018

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Anophthalmos
Teratoma
Mutation
Esophageal Atresia
Pituitary Neoplasms
Autistic Disorder
Intellectual Disability
Embryonic Development
Transcription Factors
Maintenance
Phenotype
Brain
Neoplasms

Keywords

  • anophthalmia
  • microphthalmia
  • SOX2
  • suprasellar teratoma
  • syndromic microphthalmia-3

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Extension of the mutational and clinical spectrum of SOX2 related disorders : Description of six new cases and a novel association with suprasellar teratoma. / Blackburn, Patrick R.; Chacon-Camacho, Oscar F.; Ortiz-González, Xilma R.; Reyes, Mariana; Lopez-Uriarte, Graciela A.; Zarei, Shabnam; Bhoj, Elizabeth J.; Perez-Solorzano, Sofia; Vaubel, Rachael A.; Murphree, Marine I.; Nava, Jessica; Cortes-Gonzalez, Vianney; Parisi, Joseph E; Villanueva-Mendoza, Cristina; Tirado-Torres, Iris G.; Li, Dong; Klee, Eric W; Pichurin, Pavel N.; Zenteno, Juan C.

In: American Journal of Medical Genetics, Part A, 01.01.2018.

Research output: Contribution to journalArticle

Blackburn, PR, Chacon-Camacho, OF, Ortiz-González, XR, Reyes, M, Lopez-Uriarte, GA, Zarei, S, Bhoj, EJ, Perez-Solorzano, S, Vaubel, RA, Murphree, MI, Nava, J, Cortes-Gonzalez, V, Parisi, JE, Villanueva-Mendoza, C, Tirado-Torres, IG, Li, D, Klee, EW, Pichurin, PN & Zenteno, JC 2018, 'Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma', American Journal of Medical Genetics, Part A. https://doi.org/10.1002/ajmg.a.40644
Blackburn, Patrick R. ; Chacon-Camacho, Oscar F. ; Ortiz-González, Xilma R. ; Reyes, Mariana ; Lopez-Uriarte, Graciela A. ; Zarei, Shabnam ; Bhoj, Elizabeth J. ; Perez-Solorzano, Sofia ; Vaubel, Rachael A. ; Murphree, Marine I. ; Nava, Jessica ; Cortes-Gonzalez, Vianney ; Parisi, Joseph E ; Villanueva-Mendoza, Cristina ; Tirado-Torres, Iris G. ; Li, Dong ; Klee, Eric W ; Pichurin, Pavel N. ; Zenteno, Juan C. / Extension of the mutational and clinical spectrum of SOX2 related disorders : Description of six new cases and a novel association with suprasellar teratoma. In: American Journal of Medical Genetics, Part A. 2018.
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abstract = "SOX2 is a transcription factor that is essential for maintenance of pluripotency and has several conserved roles in early embryonic development. Heterozygous loss-of-function variants in SOX2 are identified in approximately 40{\%} of all cases of bilateral anophthalmia/micropthalmia (A/M). Increasingly SOX2 mutation-positive patients without major eye findings, but with a range of other developmental disorders including autism, mild to moderate intellectual disability with or without structural brain changes, esophageal atresia, urogenital anomalies, and endocrinopathy are being reported, suggesting that the clinical phenotype associated with SOX2 loss is much broader than previously appreciated. In this report we describe six new cases, four of which carry novel pathogenic SOX2 variants. Four cases presented with bilateral anophthalmia in addition to extraocular involvement. Another individual presented with only unilateral anophthalmia. One individual did not have any eye findings but presented with a suprasellar teratoma in infancy and was found to have the recurrent c.70del20 mutation in SOX2 (c.70_89del, p.Asn24Argfs*65). This is this first time this tumor type has been reported in the context of a de novo SOX2 mutation. Notably, individuals with hypothalamic hamartomas and slow-growing hypothalamo-pituitary tumors have been reported previously, but it is still unclear how SOX2 loss contributes to their formation.",
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AU - Tirado-Torres, Iris G.

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