Genetic and structural variation in the XXXX gene in the Belgian population.

@entity1 @entity28 @entity21944 @entity146 @entity245 @entity471
OBJECTIVE: Animal studies, genome-wide association and genomic structural variation studies have identified the @entity21944 gene as a candidate gene for @entity28 . Therefore, we have designed an extensive mutation and copy number variation ( @entity471 ) analysis investigating the prevalence of genetic and structural variations in @entity21944 in the Belgian population. DESIGN AND METHODS: In the first part of this study, we performed a mutation screen for variants in the @entity21944 coding region in 581 @entity28 @entity1 and adolescents and 433 healthy, lean individuals with high-resolution melting curve analysis followed by direct sequencing. In the second part of this study, Multiplex Amplicon Quantification (MAQ) analysis was used to identify CNVs in the distal @entity21944 -containing chr.16p11.2 region in 421 @entity28 @entity1 and adolescents with no @entity245 or behavioral phenotype. RESULTS: Mutation analysis resulted in the identification of fifteen rare non-synonymous heterozygous variants. Several of these were found both in lean and @entity28 subjects, suggesting that these are neutral polymorphisms. However, six private, heterozygous, non-synonymous variations were present in @entity28 @entity1 only. Furthermore, we also identified six missense variants solely in lean individuals. @entity471 analysis could not identify carriers of the distal 16p11.2 deletion in our population. CONCLUSION: Our mutation analysis has demonstrated that variation in the @entity21944 gene is frequent in both lean and @entity28 groups, with distinctive variations being present on either side of the weight spectrum. Although the equal variation frequency does not immediately support disease causality, it cannot be excluded that some variations are weight-increasing or -decreasing. Further functional testing of the variants will be necessary to fully understand the impact of these variants on @entity21944 . We were not able to detect carriers of the distal 16p11.2 deletion in our study population. As we excluded @entity1 with developmental or @entity146 , we suggest that in addition to @entity28 , the distal deletion might predispose for these traits. Further characterization of the phenotype is therefore necessary to clearly identify the phenotype of the distal 16p11.2 microdeletion syndrome.
