Skip Navigation


Mol. Hum. Reprod. Advance Access originally published online on May 7, 2008
Molecular Human Reproduction 2008 14(6):367-370; doi:10.1093/molehr/gan027
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
14/6/367    most recent
gan027v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Pedersen-White, J. R.
Right arrow Articles by Layman, L. C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pedersen-White, J. R.
Right arrow Articles by Layman, L. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome

Jennifer R. Pedersen-White1, Lynn P. Chorich2,3,4,5, David P. Bick6,7, Richard J. Sherins8 and Lawrence C. Layman2,3,4,5,9

1Section of Endocrinology, Diabetes and Metabolism, Department of Medicine 2Section of Reproductive Endocrinology, Infertility and Genetics, Department of Obstetrics and Gynecology 3Reproductive Medicine Program 4Developmental Neurobiology Program, The Institute of Molecular Medicine and Genetics 5Neuroscience Program, The Medical College of Georgia, 1120 15th Street Augusta, GA, USA 6Department of Pediatrics, Medical College of Wisconsin, Milwaukie, WI, USA 7Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukie, WI, USA 8 Columbia Fertility Associates, Washington, DC, USA

9 Correspondence address. Tel: +1-706-721-3832; Fax: +1-706-721-6830; E-mail: llayman{at}mcg.edu

Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are clinically and genetically heterogeneous disorders caused by a deficiency of gonadotrophin-releasing hormone (GnRH). Mutations in three genes—KAL1, GNRHR and FGFR1—account for 15–20% of all causes of IHH/KS. Nearly all mutations are point mutations identified by traditional PCR-based DNA sequencing. The relatively new method of multiplex ligation-dependent probe amplification (MLPA) has been successful for detecting intragenic deletions in other genetic diseases. We hypothesized that MLPA would detect intragenic deletions in ~15–20% of our cohort of IHH/KS patients. Fifty-four IHH/KS patients were studied for KAL1 deletions and 100 were studied for an autosomal panel of FGFR1, GNRH1, GNRHR, GPR54 and NELF gene deletions. Of all male and female subjects screened, 4/54 (7.4%) had KAL1 deletions. If only anosmic males were considered, 4/33 (12.1%) had KAL1 deletions. No deletions were identified in any of the autosomal genes in 100 IHH/KS patients. We believe this to be the first study to use MLPA to identify intragenic deletions in IHH/KS patients. Our results indicate ~12% of KS males have KAL1 deletions, but intragenic deletions of the FGFR1, GNRH1, GNRHR, GPR54 and NELF genes are uncommon in IHH/KS.

Key words: Kallmann syndrome/KAL1 gene/hypogonadotropic hypogonadism/idiopathic hypogonadotropic hypogonadism/MLPA

Submitted on February 16, 2008; resubmitted on April 11, 2008; accepted on April 23, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.