title: Nail-patella syndrome: identification of mutations in the LMX1B gene in Dutch families.
abstract: Nail-patella syndrome is an autosomal dominant disorder characterized by dyplasia of finger nails, skeletal anomalies, and, frequently, renal disease. It has recently been shown that this disorder is caused by putative loss-of-function mutations in a transcription factor (LMX1B) belonging to the LIM-homeodomain family, members of which are known to be important for pattern formation during development. A cohort of eight Dutch NPS families were screened for mutations in the LMX1B gene; seven different mutations, including one novel variant, were identified. Three of the mutations are very likely to result in truncated LMX1B proteins, three are predicted to influence sequence-specific DNA binding, and one is presumed to prevent the formation of a stable protein by abolishing the Zn(II) binding site of the protein. Although there was a remarkable high incidence of renal disease in one of the families, the nephropathy was not seen in all affected family members and the severity of renal impairment varied significantly among the patients. This indicates that the incidence and severity of nephropathy within this family cannot be attributed to the LMX1B genotype. In addition, evidence of a correlation between other characteristics of the NPS phenotype and specific mutations has not been found.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: Nine V A M
authors.initials: NVAM
authors.lastname: Knoers
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: Ernie M H F
authors.initials: EMHF
authors.lastname: Bongers
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: Sylvia E C VAN
authors.initials: SECV
authors.lastname: Beersum
authors.affiliation: Department of Pediatrics, St. Joseph Hospital, Veldhoven, The Netherlands.
authors.forename: Ed J P
authors.initials: EJP
authors.lastname: Lommen
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: Hans VAN
authors.initials: HV
authors.lastname: Bokhoven
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: Frans A
authors.initials: FA
authors.lastname: Hol
mesh_terms: D001483:Base Sequence / Q000235:genetics; D015331:Cohort Studies; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications; D060850:LIM-Homeodomain Proteins; D009154:Mutation / Q000235:genetics*; D009261:Nail-Patella Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009426:Netherlands; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors