The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.
MetadataShow full item record
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.
CitationMol Hum Reprod. 2008 Jun 7; 14(6):367-370
- [Multiplex ligation dependent probe amplification analysis of KAL1, GNRH1, GNRHR, PROK2 and PROKR2 in male patients with idiopathic hypogonadotropic hypogonadism].
- Authors: Basaran Y, Bolu E, Unal HU, Sagkan RI, Taslipinar A, Ozgurtas T, Musabak U
- Issue date: 2013
- [Children with idiopathic hypogonadotropic hypogonadism: clinical data analysis and mutations analysis of KAL1 and FGFR1 gene].
- Authors: Qin M, Gong C, Qi Z, Wu D, Liu M, Gu Y, Cao B, Li W, Liang X
- Issue date: 2014 Dec
- Clinical assessment and molecular analysis of GnRHR and KAL1 genes in males with idiopathic hypogonadotrophic hypogonadism.
- Authors: Versiani BR, Trarbach E, Koenigkam-Santos M, Dos Santos AC, Elias LL, Moreira AC, Latronico AC, de Castro M
- Issue date: 2007 Feb
- Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia.
- Authors: Trarbach EB, Costa EM, Versiani B, de Castro M, Baptista MT, Garmes HM, de Mendonca BB, Latronico AC
- Issue date: 2006 Oct
- [GnRH deficiency: new insights from genetics].
- Authors: Kottler ML, Hamel A, Malville E, Richard N
- Issue date: 2004