Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Ogata, Tsutomu / Toppari, Jorma

12 Issues per year


IMPACT FACTOR 2017: 1.086

CiteScore 2017: 1.07

SCImago Journal Rank (SJR) 2017: 0.465
Source Normalized Impact per Paper (SNIP) 2017: 0.580

Online
ISSN
2191-0251
See all formats and pricing
More options …
Ahead of print

Issues

Marked phenotypic variable expression among brothers with duplication of Xq27.1 involving the SOX3 gene

Elizabeth T. Rosolowsky
  • Corresponding author
  • Division of Endocrinology, Department of Pediatrics, University of Alberta, 4-509 11405-87th Ave, Edmonton, AB Canada T6G1C9, Canada
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Robert Stein
  • Division of Pediatric Endocrinology, Schulich School of Medicine, Western University, London, Ontario, Canada
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Seth D. Marks
  • Section of Pediatric Endocrinology and Metabolism, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Norma Leonard
Published Online: 2015-08-26 | DOI: https://doi.org/10.1515/jpem-2015-0131

Abstract

We describe four phenotypically different brothers who share the same microduplication of Xq27.1, which contains the SOX3 gene. SOX3 mutations have been associated with growth hormone deficiency, variable degrees of additional pituitary hormone deficiencies, and mental retardation. SOX3 also appears to play an important role in pharyngeal arch segmentation that gives rise to craniofacial structures. While these four brothers have inherited the same mutation, they manifest a spectrum of phenotypes, ranging from complete, multiple pituitary hormone deficiencies to no apparent pituitary hormone deficiency with or without craniopharyngeal/facial dysmorphisms. We look to the literature to provide putative explanations for the variable expression of the brothers’ shared SOX3 mutation.

Keywords: congenital hypopituitarism; craniofacial dysmorphism; SOX3 gene

References

  • 1.

    de Moraes DC, Vaisman M, Conceição FL, Ortiga-Carvalho TM. Pituitary development: a complex, temporal regulated process dependent on specific transcriptional factors. J Endocrinol 2012;215:239–45.Google Scholar

  • 2.

    Nose O, Tatsumi K, Nakano Y, Amino N. Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT). J Pediatr Endocrinol Metab 2006;19:491–8.Google Scholar

  • 3.

    Zipf WB, Kelch RP, Bacon GE. Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males. Clin Genet 1977;11:249–54.PubMedCrossrefGoogle Scholar

  • 4.

    Woods KS, Cundall M, Turton J, Rizotti K, Mehta A, et al. Over- and underdosage of SOX3 is associated with infudibular hypoplasia and hypopituitarism. Am J Hum Genet 2005;76:833–49.Google Scholar

  • 5.

    Stagi S, Lapi E, Pantaleo M, Traficante G, Giglio S, et al. SOX3 (Xq26.3-27.3) duplication in a boy with growth hormone deficiency, ocular dyspraxia, and intellectual disability: a long term follow-up and literature review. Hormones (Athens) 2014;13:552–60.Google Scholar

  • 6.

    Hamel B, Smits A, Oheen BJ, van den Helm B, Ropers HH, et al. Familial X-linked mental retardation and isolated growth hormone deficiency. Am J Med Genet 1996;64:35–41.CrossrefGoogle Scholar

  • 7.

    Lagerström-Fermér M, Sundvall M, Johnsen E, Warne GL, Forrest SM, et al. X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26. Am J Hum Genet 1997;60:910–6.Google Scholar

  • 8.

    Solomon NM, Ross SA, Morgan T, Belsky JL, Hol FA, et al. Array comparative genomic hybridization analysis of boys with X-linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. J Med Genet 2004;41:669–78.Google Scholar

  • 9.

    Laumonnier F, Ronce N, Hamel BC, Thomas P, Lespinasse J, et al. Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency. Am J Hum Genet 2002;71:1450–5.Google Scholar

  • 10.

    Hol FA, Schepens MT, van Beersum SE, Redolfi E, Affer M, et al. Identification and characterization of an Xq26-27 duplication in a family with spina bifida and panhypopituitarism suggests the involvement of two distinct genes. Genomics 2000;69:174–81.Google Scholar

  • 11.

    Solomon NM, Ross SA, Forrest SM, Thomas PQ, Morgan T, et al. Array comparative genomic hybridisation analysis of boys with X-linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. (Letter) J Med Genet 2007;44:e75.Web of ScienceGoogle Scholar

  • 12.

    Bauters M, Frints SG, Van Esch H. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects. Am J Med Genet 2014;164:1947–52.Web of ScienceGoogle Scholar

  • 13.

    Alatzoglou KS, Kelberman D, Daheani MT. The role of SOX proteins in normal pituitary development. J Endocrinol 2009;200:245–58.Google Scholar

  • 14.

    Moalem S, Babul-Hirji R, Stavropolous DJ, Wherrett D, Bagli DJ, et al. XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication. Am J Med Genet A 2012;158A;1759–64.Google Scholar

  • 15.

    Rizzoti K, Brunelli S, Carmignac D, Thomas PQ, Robinson IC, et al. SOX3 is required during the formation of the hypothalamo-pituitary axis. Nat Genet 2004;36:247–55.CrossrefGoogle Scholar

  • 16.

    Rizzoti K, Lovell-Badge R. SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis. Development 2007;134:3437–48.Web of ScienceGoogle Scholar

  • 17.

    Wegner M, Stolt CC. From stem cells to neurons and glia: a Soxist’s view of neural development. Trends Neurosci 2005;28:583–8.CrossrefGoogle Scholar

  • 18.

    Tziaferi V, Kelberman D, Dattani MT. The role of SOX2 in hypogonadotropic hypogonadism. Sex Dev 2008;2:194–9.CrossrefGoogle Scholar

About the article

Corresponding author: Elizabeth T. Rosolowsky, Division of Endocrinology, Department of Pediatrics, University of Alberta, 4-509 11405-87th Ave, Edmonton, AB Canada T6G1C9, Canada, Phone: +780-248-5483, Fax: +888-775-8879, E-mail:


Received: 2015-03-25

Accepted: 2015-07-17

Published Online: 2015-08-26


Citation Information: Journal of Pediatric Endocrinology and Metabolism, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2015-0131.

Export Citation

©2015 by De Gruyter.Get Permission

Comments (0)

Please log in or register to comment.
Log in