Cytogenetic analysis and detection of KAL-1 gene deletion with fluorescence in situ hybridization (FISH) in patients with Kallmann syndrome

Trarbach, Ericka Barbosa; Baptista, Mónica; Maciel‐Guerra, Andréa Trevas; Hackel, Christine

doi:10.1590/s0004-27302001000600008

Cited by 2 publications

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“…We have previously identified three other KAL-1 abnormalities in this series of Brazilian KS patients: in a sporadic case (KS1) a KAL-1 gene microdeletion was detected by fluorescence in situ hybridization, while in two families with X-linked inheritance (patients KS2 and KS7) similar intragenic deletions of exons 5-10 were found after PCR analysis (Trarbach et al 2001(Trarbach et al , 2004. Thus, the prevalence of KAL1 mutations in these Brazilian patients was 100% in the familial X-linked KS (three of three families) and 30% in sporadic cases (two of seven).…”

Section: Discussionmentioning

confidence: 85%

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

Trarbach¹,

Baptista²,

Garmes³

et al. 2005

Journal of Endocrinology

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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.

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Section: Discussionmentioning

confidence: 85%

“…Molecular analysis of the KAL-1 gene was initially carried out both in KS and nHH patients; exceptions were made for the three KS patients (KS1, KS2 and KS7) in which genotypes have been previously described (Trarbach et al 2001(Trarbach et al , 2004. The five nHH patients were further screened for mutations in the GnRH-R gene.…”

Section: Methodsmentioning

confidence: 99%