The Hippo pathway is a highly conserved signalling route involved in organ size regulation. The final effectors of this pathway are two transcriptional coactivators, yes-associated protein (YAP)... Show moreThe Hippo pathway is a highly conserved signalling route involved in organ size regulation. The final effectors of this pathway are two transcriptional coactivators, yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (WWTR1 or TAZ). Previously, we showed aberrant activation of the Hippo pathway in autosomal-dominant polycystic kidney disease (ADPKD), suggesting that YAP/TAZ might play a role in disease progression. Using antisense oligonucleotides (ASOs) in a mouse model for ADPKD, we efficiently down-regulatedYaplevels in the kidneys. However, we did not see any effect on cyst formation or growth. Moreover, the expression of YAP/TAZ downstream targets was not changed, while WNT and TGF-beta pathways' downstream targetsMyc,Acta2andVimwere more expressed afterYapknockdown. Overall, our data indicate that reducing YAP levels is not a viable strategy to modulate PKD progression. Show less
Dauwerse, J.G.; Dixon, J.; Seland, S.; Ruivenkamp, C.A.L.; Haeringen, A. van; Hoefsloot, L.H.; ... ; Wieczorek, D. 2011
We identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional... Show moreWe identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional heterozygous mutations of POLR1D in 252 individuals with TCS. Furthermore, we discovered mutations in both alleles of POLR1C in three individuals with TCS. These findings identify two additional genes involved in TCS, confirm the genetic heterogeneity of TCS and support the hypothesis that TCS is a ribosomopathy. Show less
Dauwerse, J.G.; Dixon, J.; Seland, S.; Ruivenkamp, C.A.L.; Haeringen, A. van; Hoefsloot, L.H.; ... ; Wieczorek, D. 2011
We have characterized a de novo complex rearrangement of the long arm of chromosome 7 in a female patient with moderate mental retardation (MR), anxiety disorder, and autistic features. G-banding... Show moreWe have characterized a de novo complex rearrangement of the long arm of chromosome 7 in a female patient with moderate mental retardation (MR), anxiety disorder, and autistic features. G-banding suggested a de novo paracentric inversion 46,XX,inv-(7) (q31.3q34). However, SNP-array analysis, showed a +/-10 Mb, 7q21.11-q21.3 deletion in the paternal chromosome. Subsequent FISH analysis with BAC/PAC clones in the 7q21-q35 region confirmed this deletion. However, the expected paracentric inversion turned out to be an intra-chromosomal insertion of the 7q31.31-q35 fragment into band 7q21.3, disrupting the predicted gene C7orf58 in band 7q31.31. Seven other patients have been previously reported with a deletion of 7q21.1-q21.3. Although there is an overlap in phenotype between our patient and these patients, none of them has been described with anxiety disorder and/or autistic features. Therefore we suggest that disruption of the C7orf58 gene might contribute to the anxiety disorder, and autistic features in our patient. (C) 2010 Wiley-Liss, Inc. Show less
We have characterized a de novo complex rearrangement of the long arm of chromosome 7 in a female patient with moderate mental retardation (MR), anxiety disorder, and autistic features. G-banding... Show moreWe have characterized a de novo complex rearrangement of the long arm of chromosome 7 in a female patient with moderate mental retardation (MR), anxiety disorder, and autistic features. G-banding suggested a de novo paracentric inversion 46,XX,inv(7)(q31.3q34). However, SNP-array analysis, showed a +/-10 Mb, 7q21.11-q21.3 deletion in the paternal chromosome. Subsequent FISH analysis with BAC/PAC clones in the 7q21-q35 region confirmed this deletion. However, the expected paracentric inversion turned out to be an intra-chromosomal insertion of the 7q31.31-q35 fragment into band 7q21.3, disrupting the predicted gene C7orf58 in band 7q31.31. Seven other patients have been previously reported with a deletion of 7q21.1-q21.3. Although there is an overlap in phenotype between our patient and these patients, none of them has been described with anxiety disorder and/or autistic features. Therefore we suggest that disruption of the C7orf58 gene might contribute to the anxiety disorder, and autistic features in our patient. Show less
