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

Hdl Handle:
http://hdl.handle.net/10675.2/141
Title:
The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.
Authors:
Pedersen-White, Jennifer R; Chorich, Lynn P; Bick, David P ( 0000-0002-8750-306X ) ; Sherins, Richard J; Layman, Lawrence C
Abstract:
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 approximately 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 approximately 12% of KS males have KAL1 deletions, but intragenic deletions of the FGFR1, GNRH1, GNRHR, GPR54 and NELF genes are uncommon in IHH/KS.
Citation:
Mol Hum Reprod. 2008 Jun 7; 14(6):367-370
Issue Date:
23-Jun-2008
URI:
http://hdl.handle.net/10675.2/141
DOI:
10.1093/molehr/gan027
PubMed ID:
18463157
PubMed Central ID:
PMC2434956
Type:
Journal Article; Research Support, N.I.H., Extramural
ISSN:
1460-2407
Appears in Collections:
Department of Medicine Faculty: Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorPedersen-White, Jennifer Ren_US
dc.contributor.authorChorich, Lynn Pen_US
dc.contributor.authorBick, David Pen_US
dc.contributor.authorSherins, Richard Jen_US
dc.contributor.authorLayman, Lawrence Cen_US
dc.date.accessioned2010-09-24T22:03:26Z-
dc.date.available2010-09-24T22:03:26Z-
dc.date.issued2008-06-23en_US
dc.identifier.citationMol Hum Reprod. 2008 Jun 7; 14(6):367-370en_US
dc.identifier.issn1460-2407en_US
dc.identifier.pmid18463157en_US
dc.identifier.doi10.1093/molehr/gan027en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/141-
dc.description.abstractIdiopathic 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 approximately 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 approximately 12% of KS males have KAL1 deletions, but intragenic deletions of the FGFR1, GNRH1, GNRHR, GPR54 and NELF genes are uncommon in IHH/KS.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAdolescenten_US
dc.subject.meshCohort Studiesen_US
dc.subject.meshExtracellular Matrix Proteins / geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Deletionen_US
dc.subject.meshGene Frequencyen_US
dc.subject.meshGonadotropin-Releasing Hormone / geneticsen_US
dc.subject.meshHeterozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshHypogonadism / complications / geneticsen_US
dc.subject.meshKallmann Syndrome / geneticsen_US
dc.subject.meshMaleen_US
dc.subject.meshNerve Tissue Proteins / geneticsen_US
dc.subject.meshOlfaction Disorders / complications / geneticsen_US
dc.subject.meshProtein Precursors / geneticsen_US
dc.subject.meshReceptor, Fibroblast Growth Factor, Type 1 / geneticsen_US
dc.subject.meshReceptors, G-Protein-Coupled / geneticsen_US
dc.subject.meshReceptors, LHRH / geneticsen_US
dc.subject.meshSex Characteristicsen_US
dc.subject.meshTranscription Factors / geneticsen_US
dc.titleThe prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.identifier.pmcidPMC2434956en_US
dc.contributor.corporatenameDepartment of Medicineen_US
dc.contributor.corporatenameDepartment of Obstetrics and Gynecologyen_US
dc.contributor.corporatenameDepartment of Obstetrics and Gynecologyen_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Geneticsen_US
dc.contributor.corporatenameInstitute of Neuroscienceen_US

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