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

Jennifer R. Pedersen-White, Lynn P. Chorich, David P. Bick, Richard J. Sherins, Lawrence C Layman

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)367-370
Number of pages4
JournalMolecular Human Reproduction
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2008

Fingerprint

Kallmann Syndrome
Multiplex Polymerase Chain Reaction
Genes
Mutation
Inborn Genetic Diseases
Idiopathic Hypogonadotropic Hypogonadism
Gene Deletion
DNA Sequence Analysis
Point Mutation
Gonadotropin-Releasing Hormone
Polymerase Chain Reaction

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

Cite this

The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. / Pedersen-White, Jennifer R.; Chorich, Lynn P.; Bick, David P.; Sherins, Richard J.; Layman, Lawrence C.

In: Molecular Human Reproduction, Vol. 14, No. 6, 01.06.2008, p. 367-370.

Research output: Contribution to journalArticle

Pedersen-White, Jennifer R. ; Chorich, Lynn P. ; Bick, David P. ; Sherins, Richard J. ; Layman, Lawrence C. / The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. In: Molecular Human Reproduction. 2008 ; Vol. 14, No. 6. pp. 367-370.
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