ESPE Abstracts

Background: The WDR11 gene was recently involved in the pathogenesis of isolated hypogonadotropic hypogonadism (IHH). In 2010, Kim et al. (1) identified five different heterozygous missense WDR11 rare variants in six of 201 IHH patients (five normosmic IHH and one Kallmann syndrome), which were absent in more than 400 controls. Animal studies demonstrated that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and the missense alterations reduced or abolished this interaction. However, since this first description, no other mutations in this gene were associated with the IHH phenotype.

Objective and hypotheses: To investigate the presence of WDR11 rare variants in patients with IHH with and without olfatctory defects.

Method: We studied 129 Brazilian patients with sporadic or familial IHH, including 65 with normosmic IHH and 64 with Kallmann syndrome. Genomic DNA was extracted from peripheral leukocytes from all patients. All 29 exons and exon–intron boundary regions of WDR11 were amplified by PCR using specific primer pairs and automatically sequenced.

Results: No rare variants were identified in the patients studied. Only known polymorphisms were found: rs35692153, COSM147066, rs151162552, rs7899928, COSM147068, rs34567350, rs1652727, rs34567350, COSM147069, rs149486212, rs117848117, COSM1346180, and rs12268298.

Conclusion: These results show that WDR11 rare variants are not a common cause of IHH, and suggest that the role of this gene in the pathogenesis of this condition needs to be further investigated.