• PMID: 18463157
• Gene Name: KAL1
• Condition: Idiopathic hypogonadotropic hypogonadism, Kallmann syndrome
• Association: The 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
• Population size: 154
• Population details: 154 (54 IHH/KS, 100 controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: FGFR1, GNRH1, KAL1, GNRHR, GPR54 and NELF
• Other associated phenotypes: Idiopathic hypogonadotropic hypogonadism, Kallmann syndrome

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

Pedersen-White JR, Chorich LP, Bick DP, Sherins RJ, Layman LC.

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. FAU - Pedersen-White, Jennifer R AU - Pedersen-White JR AD - Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Medical College of Georgia, Augusta, GA, USA. FAU - Chorich, Lynn P AU - Chorich LP FAU - Bick, David P AU - Bick DP FAU - Sherins, Richard J AU - Sherins RJ