Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF ) Freely available
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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 ISI Web of Science
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
Right arrow Search for citing articles in:
ISI Web of Science (22)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Allen, L. A.
Right arrow Articles by Ball, S. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allen, L. A.
Right arrow Articles by Ball, S. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Reproduction, Vol. 18, No. 2, 251-256, February 2003
© 2003 European Society of Human Reproduction and Embryology

A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics

Linda A. Allen1, John C. Achermann2,3, Pirjo Pakarinen4, Thomas J. Kotlar2, Ilpo T. Huhtaniemi4, J. Larry Jameson2, Tim D. Cheetham1,5 and Stephen G. Ball1

1 School of Clinical Medical Sciences, University of Newcastle NE2 4HH, UK, 2 Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, IL 60611, USA, 3 Centre for Human Growth and Maturation, Department of Medicine and Institute of Child Health, University College London, London WC1N 1EH, UK and 4 Department of Physiology, University of Turku, Turku, FIN-20520, Finland

5 To whom correspondence should be addressed at: Department of Paediatrics, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK. e-mail: t.d.cheetham{at}ncl.ac.uk

BACKGROUND: Inactivating mutations of the FSH receptor (FSHR) are a rare cause of hypergonadotrophic hypogonadism in women. Only one patient with primary amenorrhoea due to an FSHR gene mutation has been reported outside of Finland, where the prevalence of Ala189Val mutations is particularly high. METHODS AND RESULTS: Here, we describe the clinical, molecular genetic and functional characteristics associated with a novel inactivating mutation in exon 10 of the FSHR gene identified in a patient who presented with primary amenorrhoea at 17 years of age. The C to G transversion found at nucleotide 1043 causes a Pro348Arg substitution in the extracellular region of the FSHR and results in a mutant FSHR that is completely inactive in functional studies and that does not bind FSH. The proband exhibits apparent homozygosity for this recessive mutation. Her father is heterozygous for the mutation while analysis of exon 10 of the FSHR gene from her mother revealed only wild-type sequence. Chromosome painting was used to exclude deletions or rearrangements of 2p, and microsatellite markers did not show paternal uniparental isodisomy for this region. These findings suggest that the proband is hemizygous, with an inherited or de-novo microdeletion, or alternatively a de-novo gene conversion, of the accompanying FSHR allele. CONCLUSIONS: This case confirms the importance of the FSHR in female pubertal development and reproduction, and supports a relationship between phenotype and function for FSHR mutations.

Key words: FSH/FSH receptor/infertility/ovary/puberty


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


This article has been cited by other articles:


Home page
 Mol Hum ReprodHome page
M. Ghadami, S.A. Salama, N. Khatoon, R. Chilvers, M. Nagamani, P.J. Chedrese, and A. Al-Hendy
Toward gene therapy of primary ovarian failure: adenovirus expressing human FSH receptor corrects the Finnish C566T mutation
Mol. Hum. Reprod., January 1, 2008; 14(1): 9 - 15.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
V. Sundblad, V. A. Chiauzzi, L. Andreone, S. Campo, E. H. Charreau, and L. Dain
Controversial role of inhibin {alpha}-subunit gene in the aetiology of premature ovarian failure
Hum. Reprod., May 1, 2006; 21(5): 1154 - 1160.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
C. M. Allan, A. Garcia, J. Spaliviero, M. Jimenez, and D. J. Handelsman
Maintenance of Spermatogenesis by the Activated Human (Asp567Gly) FSH Receptor During Testicular Regression Due to Hormonal Withdrawal
Biol Reprod, May 1, 2006; 74(5): 938 - 944.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
A. P N Themmen
An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms
Reproduction, September 1, 2005; 130(3): 263 - 274.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
N. Massin, A. Gougeon, G. Meduri, E. Thibaud, K. Laborde, C. Matuchansky, E. Constancis, M.C. Vacher-Lavenu, B. Paniel, J.R. Zorn, et al.
Significance of ovarian histology in the management of patients presenting a premature ovarian failure
Hum. Reprod., November 1, 2004; 19(11): 2555 - 2560.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. M. Monick, R. K. Mallampalli, M. Bradford, D. McCoy, T. J. Gross, D. M. Flaherty, L. S. Powers, K. Cameron, S. Kelly, A. H. Merrill Jr., et al.
Cooperative Prosurvival Activity by ERK and Akt in Human Alveolar Macrophages is Dependent on High Levels of Acid Ceramidase Activity
J. Immunol., July 1, 2004; 173(1): 123 - 135.
[Abstract] [Full Text] [PDF]


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.