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 ∼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.
Original language | English (US) |
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Pages (from-to) | 367-370 |
Number of pages | 4 |
Journal | Molecular Human Reproduction |
Volume | 14 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2008 |
Keywords
- Hypogonadotropic hypogonadism
- Idiopathic hypogonadotropic hypogonadism
- KAL1 gene
- Kallmann syndrome
- MLPA
ASJC Scopus subject areas
- Reproductive Medicine
- Embryology
- Molecular Biology
- Genetics
- Obstetrics and Gynecology
- Developmental Biology
- Cell Biology