• PMID: 16423815
• Gene Name: EBF2
• Condition: Normosmic hypogonadotropic hypogonadism
• Association: 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 g
• Mutation: KAL1 ((del1956C) in exon 12, 191 (Arg191X))
• Population size: 17
• Population details: 17 (12 Kallmann syndrome (KS), 5 normosmic hypogonadotropic hypogonadism (nHH) )
• Sex: Male
• Infertility type: Male infertility
• Associated genes: KAL-1, NELF and EBF2
• Other associated phenotypes: Normosmic hypogonadotropic hypogonadism

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

Trarbach EB, Baptista MT, Garmes HM, Hackel C.

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. FAU - Trarbach, Ericka B AU - Trarbach EB AD - Laboratório de Genética Humana, Centro de Biologia Molecular e Engenharia Genética (CBMEG), UNICAMP, Campinas, 13083970, São Paulo, Brazil. trarbach@hotmail.com FAU - Baptista, Maria T M AU - Baptista MT FAU - Garmes, Heraldo M AU - Garmes HM