Confirmation of CLIM2/LMX1B interaction by yeast two-hybrid screening and analysis of its involvement in nail-patella syndrome

被引:1
作者
Marini, M
Bongers, EMHF
Cusano, R
Di Duca, M
Seri, M
Knoers, NVAM
Ravazzolo, R
机构
[1] Ist Giannina Gaslini, Genet Mol Lab, I-16148 Genoa, Italy
[2] Univ Genoa, Dipartimento Pediat, Genoa, Italy
[3] Univ Bologna, Policlin S Orsola Malpighi, UO Genet Med, Dipartimento Med Interna Cardioangiol & Epatol, I-40138 Bologna, Italy
[4] Ist Giannina Gaslini, Lab Nefrol, I-16148 Genoa, Italy
[5] Univ Med Ctr Nijmegen, Dept Human Genet, Nijmegen, Netherlands
关键词
nail-patella syndrome; nephropathy; LMX1B gene;
D O I
暂无
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Nail-patella syndrome (NPS), an autosomal dominant disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and often associated with nephropathy and, less frequently, with open angle glaucoma, is caused by mutations in the LMX1B gene. Inter-familial and intra-familial phenotypic variability raises the question whether modifier genes can be identified to explain differences in the expression and severity of clinical features of NPS. Genes encoding proteins that interact with the LMX1B protein are good candidates and, therefore, methods to search for interactions can be used to this purpose. By the yeast two-hybrid screening we detected the CLIM2 gene as a LMX1B interactor, confirming previous reports which described the same interaction by biochemical methods. Sequencing of the CLIM2 coding region in seven NPS cases in which no LMX1B mutation had been found, did not detect any molecular variant in these patients. Moreover, by genotyping a polymorphic dinucleotide repeat close to the CLIM2 gene in affected members of a large Dutch NPS family with high incidence of nephropathy, we were unable to find a correlation between the presence of a specific allele and the expression of nephropathy. In conclusion, although the results of this study could not provide any proof of CLIM2 involvement in the pathogenesis of NPS or in determination of the clinical phenotype, we suggest that the CLIM2 gene can be considered as a good candidate for further studies on normal and disturbed kidney development associated with NPS or orther hereditary glomerulopathies.
引用
收藏
页码:79 / 82
页数:4
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