Abstract | CONTEXT: OBJECTIVE: The present study aimed at identifying DAX1 mutations in Chinese AHC patients and investigating the functional defects of detected novel mutations. PATIENTS AND METHODS: Nine patients with AHC were recruited from eight families. DAX1 mutations were screened, and the transcriptional activities of the identified mutations were assessed in vitro. RESULTS: DAX1 mutations were detected in all nine patients enrolled in the study, with eight different mutations. Among the latter, seven are novel mutations, including two missense (L262P and C368F), one nonsense (Q222X), and four frame-shift (637delC, 652_653delAC, 973delC, and 774_775insCC) mutations. The functional studies showed that the mutant DAX1 was impaired by nuclear localization, loss of trans-repression of StAR and LHbeta transcriptional activities, and reduction of GnRH expression. CONCLUSION: These findings provide insight into the molecular events by which DAX1 mutations influence the hypothalamus-pituitary-gonadal and hypothalamus-pituitary-adrenal axis and lead to AHC and hypogonadotropic hypogonadism.
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Authors | Na Li, Ruya Liu, Huijie Zhang, Jun Yang, Shouyue Sun, Manna Zhang, Yuejun Liu, Yan Lu, Wei Wang, Yiming Mu, Guang Ning, Xiaoying Li |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 95
Issue 9
Pg. E104-11
(Sep 2010)
ISSN: 1945-7197 [Electronic] United States |
PMID | 20573681
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DAX-1 Orphan Nuclear Receptor
- NR0B1 protein, human
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Topics |
- Adolescent
- Adrenal Insufficiency
(complications, congenital, genetics)
- Adult
- Asian People
(genetics)
- Child
- Child, Preschool
- DAX-1 Orphan Nuclear Receptor
(genetics, physiology)
- DNA Mutational Analysis
- Family
- Female
- Genetic Testing
- Humans
- Hypogonadism
(complications, congenital, genetics)
- Infant
- Infant, Newborn
- Male
- Mutation
(physiology)
- Young Adult
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