Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann syndrome and normosmic hypogonadotropic hypogonadism patients.

Abstract

We report the results of molecular analysis in a series of twelve Kallmann syndrome (KS) and five normosmic hypogonadotropic hypogonadism (nHH) Brazilian patients. Kallman syndrome 1 (KAL-1) gene analysis was performed in all patients and the gonadotrophin releasing hormone receptor (GnRH-R) gene was investigated in nHH patients using PCR analysis with exon-flanking primers followed by automated sequencing techniques. Two-point mutations at the KAL-1 locus were found in two KS patients. One case exhibited a novel C deletion (del1956C) in exon 12 leading to a premature stop codon at position 617. The second case, a C to T transition at exon 5, showed a stop codon at aminoacid 191 (Arg191X). Renal agenesis and bimanual synkinesis, which are frequently found in patients with the KAL-1 mutation, were observed in these cases. Among the KS patients, two previously reported cases had intragenic deletions of exons 5-10, while a third patient had a KAL-1 gene microdeletion detected by fluorescence in situ hybridization. For the nHH patients, no abnormalities were observed at the exonic and flanking sequences of the KAL-1 or GnRH-R genes. Nasal embryonic LHRH factor (NELF) and early B-cell factor 2 (EBF2) exons were evaluated in KAL-1/GnRH-R mutation-negative cases (seven KS and five nHH) by sequence analysis but no mutations were identified in the coding regions in these patients. In conclusion, this report includes the description of a novel point mutation of the KAL-1 gene and suggests that the KAL-1 mutations and deletions might be more prevalent in KS Brazilian patients than previously described in other series. NELF and EBF2 genes have been considered good candidates for HH and a large number of patients need to be studied to assess their contribution to reproductive function.

• Authors: Ericka B Trarbach, Maria T M Baptista, Heraldo M Garmes, Christine Hackel
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 187 Issue 3 Pg. 361-8 (Dec 2005) ISSN: 0022-0795 [Print] England
• PMID: 16423815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ANOS1 protein, human
• Amino Acids
• Basic Helix-Loop-Helix Transcription Factors
• EBF2 protein, human
• Extracellular Matrix Proteins
• GNRHR protein, human
• NSMF protein, human
• Nerve Tissue Proteins
• Receptors, LHRH
• Transcription Factors

Topics

• Amino Acids (genetics)
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Exons (genetics)
• Extracellular Matrix Proteins (genetics)
• Gene Deletion
• Humans
• Hypogonadism (genetics)
• Kallmann Syndrome (genetics)
• Male
• Nerve Tissue Proteins (genetics)
• Point Mutation (genetics)
• Polymorphism, Genetic (genetics)
• Receptors, LHRH (genetics)
• Sequence Analysis, DNA (methods)
• Transcription Factors (genetics)