ECTS Abstracts (2015) 1 P243

Genetic Screening of WNT5B in Patients with Monogenic Sclerosing Bone Disorders and Healthy Men with an Extreme Bone Mineral Density

Gretl Hendrickx1, Eveline Boudin1, Leo Torben Nielsen2, Marianne Andersen2, Kim Brixen2 & Wim Van Hul1

1Department of Medical Genetics, University of Antwerp, Antwerp, Belgium; 2Department of Endocrinology, Odense University Hospital, Odense, Denmark.

The past decade, genome wide association studies (GWAS) have been performed to reveal the links between genomic variation and the occurrence of osteoporosis. These studies revealed the WNT5B gene, being associated with bone mineral density (BMD) at the level of the femoral neck and the lumbar spine with genome-wide significance (p< 5x10−8). This finding made WNT5B interesting for further genetic studies to verify the influence of common and rare genetic variation in this gene in patients with high BMD disorders and on the BMD of healthy individuals. First, a mutation screening was performed in a population of patients with monogenic sclerosing bone disorders (n=43), which all tested negative for mutations in the known causative genes (SOST, LRP5 and LRP4). All coding exons of WNT5B and their intron-exon boundaries were analysed by using Sanger sequencing. Here, WNT5B showed no disease-causing mutations. Moreover, re-sequencing of WNT5B was performed on healthy men of the Odense Androgen Study (OAS). Here, based on their extreme high or low BMD values, two cohorts of 63 subjects each were selected. Again, all coding exons and their intron-exon boundaries were screened for rare and common variation using Sanger sequencing. As a result, no coding variation could be detected in the WNT5B gene. Five intronic variants were detected to be varying across the cohorts, but showed no significant difference in genotype frequencies between the lower and higher BMD cohort. Despite the results from GWAS in the past, we were not able to replicate or further verify an important role for WNT5B in the genetic determination of BMD.

Disclosure: The authors declared no competing interests.

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