1. Mutation of WIF1: a potential novel cause of a Nail-Patella-like disorder
- Author
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Manuel Rueda, Emily G. Spencer, Tierney Phillips, Marilyn C. Jones, Sarah E. Topol, Glenn Oliveira, and Ali Torkamani
- Subjects
0301 basic medicine ,musculoskeletal diseases ,Adult ,Male ,Turner-Kieser syndrome ,medicine.medical_specialty ,Adolescent ,LIM-Homeodomain Proteins ,WIF1 ,Kidney ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Nail-Patella Syndrome ,medicine ,Humans ,skin and connective tissue diseases ,nail dysplasia ,Genetics (clinical) ,Exome sequencing ,Nail patella syndrome ,Adaptor Proteins, Signal Transducing ,Aged ,Genetics ,integumentary system ,business.industry ,Brief Report ,Genetic disorder ,Kidney metabolism ,Patella ,Fong disease ,medicine.disease ,musculoskeletal system ,Dermatology ,Phenotype ,3. Good health ,Pedigree ,Repressor Proteins ,030104 developmental biology ,medicine.anatomical_structure ,Mutation (genetic algorithm) ,Mutation ,Nail (anatomy) ,Female ,business ,HOOD syndrome ,Transcription Factors - Abstract
Purpose: Nail-Patella syndrome is a dominantly inherited genetic disorder characterized by abnormalities of the nails, knees, elbows, and pelvis. Nail abnormalities are the most constant feature of Nail-Patella syndrome. Pathogenic mutations in a single gene, LMX1B, a mesenchymal determinant of dorsal-ventral patterning, explain approximately 95% of Nail-Patella syndrome cases. However, 5% of cases remain unexplained. Methods: Here, we present exome sequencing and analysis of four generations of a family with a dominantly inherited Nail-Patella-like disorder (nail dysplasia with some features of Nail-Patella syndrome) who tested negative for LMX1B mutation. Results: We identify a loss-of-function mutation in WIF1 (NM_007191 p.W15*), which is involved in mesoderm segmentation, as the suspected cause of the Nail-Patella-like disorder observed in this family. Conclusions: Mutation of WIF1 is a potential novel cause of a Nail-Patella-like disorder. Testing of additional patients negative for LMX1B mutation is needed to confirm this finding and further clarify the phenotype. Genet Med advance online publication 06 April 2017
- Published
- 2016