NDLI: OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hoshino, Masaya Ishizu, Katsura Amemiya, Shin Ohtake, Akira Fujieda, Kenji Sasaki, Nozomu Tajima, Toshihiro
Description	Author Affiliation: Tajima T ( Department of Pediatrics, Hokkaido University School of Medicine, N15, W7, Sapporo, Japan 060-0835. tajeari@hokudai.med.ac.jp)
Abstract	CONTEXT: Orthodenticle homeobox 2 (OTX2) is a transcription factor necessary for ocular and forebrain development. In humans, heterozygous mutations of OTX2 cause severe ocular malformations. However, whether mutations of OTX2 cause pituitary structural abnormalities or combined pituitary hormone deficiency (CPHD) has not been clarified. OBJECTIVES: We surveyed the functional consequences of a novel OTX2 mutation that was detected in a patient with anophthalmia and CPHD. PATIENT: We examined a Japanese patient with growth disturbance, anophthalamia, and severe developmental delay. He showed deficiencies in GH, TSH, LH, FSH, and ACTH. Brain magnetic resonance imaging revealed a small anterior pituitary gland, invisible stalk, ectopic posterior lobe, and Chiari malformation. RESULTS: Sequence analysis of OTX2 demonstrated a heterozygous two bases insertion [S136fsX178 (c.576-577insCT)] in exon 3. The mutant Otx2 protein localized to the nucleus, but did not activate the promoter of the HESX1 and POU1F1 gene, indicating a loss of function mutation. No dominant negative effect in the presence of wild-type Otx2 was observed. CONCLUSION: This case indicates that the OTX2 mutation is a cause of CPHD. Further study of more patients with OTX2 defects is necessary to clarify the clinical phenotypes and endocrine defects caused by OTX2 mutations.
ISSN	0021972X
e-ISSN	19457197
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	1
Volume Number	94
Language	English
Publisher	Oxford University Press
Publisher Date	2009-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Anophthalmos Genetics Choristoma Mutation Otx Transcription Factors Pituitary Gland, Anterior Pituitary Gland, Posterior Abnormalities Pituitary Hormones Deficiency Animals Cos Cells Cercopithecus Aethiops Magnetic Resonance Imaging Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article Case study
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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