Multiplex ligation dependent probe amplification analysis of KAL1, GNRH1, GNRHR, PROK2 and PROKR2 in male patients with idiopathic hypogonadotropic hypogonadism

Endokrynol Pol. 2013;64(4):285-92. doi: 10.5603/ep.2013.0007.

Abstract

Introduction: The purpose of this study was to determine the prevalence of KAL1, GNRH1, GNRHR, PROK2, and PROKR2 copy numbervariations in patients with idiopathic hypogonadotropic hypogonadism (IHH).

Material and methods: 86 hypogonadal males (76 diagnosed with normosmic idiopathic hypogonadotropic hypogonadism [nIHH] andten with Kallmann syndrome [KS]) and 95 healthy control individuals were studied for the presence of aforementioned genomic rearrangements,using multiplex ligation dependent probe amplification (MLPA).

Results: We detected that of the 86 patients, three with KS had a deletion of the KAL1 gene in exon 9, one of whom also carried a duplicationin exon 11; and three with nIHH had a duplication of the PROK2 gene in exon 3; a deletion of the GNRHR gene in exon 1; anda duplication of the same gene in exon 2, respectively. No abnormalities were found in the patient group for the PROKR2 and GNRH1genes. In addition, no genomic rearrangements were identified in the healthy control individuals for the described genes.

Conclusions: Defining the genetic basis of disease is essential to improve our understanding of this complex disorder, and could be usefulfor genetic counselling and for directing therapy. In addition, discovering the association between genetic mutations and disease isimportant for our better understanding of normal reproductive functions.

MeSH terms

  • Extracellular Matrix Proteins / genetics*
  • Gene Deletion
  • Gene Frequency
  • Gonadotropin-Releasing Hormone / genetics*
  • Humans
  • Hypogonadism / diagnosis
  • Hypogonadism / genetics*
  • Male
  • Nerve Tissue Proteins / genetics*
  • Nucleic Acid Amplification Techniques / methods
  • Protein Precursors / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Receptors, LHRH / genetics*

Substances

  • ANOS1 protein, human
  • Extracellular Matrix Proteins
  • GNRHR protein, human
  • Nerve Tissue Proteins
  • Protein Precursors
  • Receptors, LHRH
  • progonadoliberin I
  • Gonadotropin-Releasing Hormone
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1