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|Title:||Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism|
|Citation:||American Journal of Human Genetics, 2005; 76(5):833-849|
|Publisher:||Univ Chicago Press|
|Kathryn S. Woods, Maria Cundall, James Turton, Karine Rizotti, Ameeta Mehta, Rodger Palmer, Jacqueline Wong, W. K. Chong, Mahmoud Al-Zyoud, Maryam El-Ali, Timo Otonkoski, Juan-Pedro Martinez-Barbera, Paul Q. Thomas, Iain C. Robinson, Robin Lovell-Badge, Karen J. Woodward and Mehul T. Dattani|
|Abstract:||Duplications of Xq26-27 have been implicated in the etiology of X-linked hypopituitarism associated with mental retardation (MR). Additionally, an expansion of a polyalanine tract (by 11 alanines) within the transcription factor SOX3 (Xq27.1) has been reported in patients with growth hormone deficiency and variable learning difficulties. We report a submicroscopic duplication of Xq27.1, the smallest reported to date (685.6 kb), in two siblings with variable hypopituitarism, callosal abnormalities, anterior pituitary hypoplasia (APH), an ectopic posterior pituitary (EPP), and an absent infundibulum. This duplication contains SOX3 and sequences corresponding to two transcripts of unknown function; only Sox3 is expressed in the infundibulum in mice. Next, we identified a novel seven-alanine expansion within a polyalanine tract in SOX3 in a family with panhypopituitarism in three male siblings with an absent infundibulum, severe APH, and EPP. This mutation led to reduced transcriptional activity, with impaired nuclear localization of the mutant protein. We also identified a novel polymorphism (A43T) in SOX3 in another child with hypopituitarism. In contrast to findings in previous studies, there was no evidence of MR or learning difficulties in our patients. We conclude that both over- and underdosage of SOX3 are associated with similar phenotypes, consisting of infundibular hypoplasia and hypopituitarism but not necessarily MR.|
|Description:||© 2005 by The American Society of Human Genetics|
|Appears in Collections:||Aurora harvest 5|
Molecular and Biomedical Science publications
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