Evidence for Increased SOX3 Dosage as a Risk Factor for X-Linked Hypopituitarism and Neural Tube Defects

Marijke Bauters, Suzanna G. Frints, Hilde Van Esch, Liesbeth Spruijt, Marcella M. Baldewijns, Christine E. M. de Die-Smulders, Jean-Pierre Fryns, Peter Marynen, Guy Froyen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X; 22)(q27; q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects.
Original languageEnglish
Pages (from-to)1947-1952
JournalAmerican Journal of Medical Genetics Part A
Issue number8
Publication statusPublished - Aug 2014


  • X-linked hypopituitarism
  • growth hormone deficiency
  • SOX3 duplication
  • neural tube defect
  • gene overexpression

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