title: Novel LMX1B mutation in familial nail-patella syndrome with variable expression of open angle glaucoma.
abstract: OBJECTIVE
  To describe the genetic and clinical findings in a large Spanish pedigree with nail-patella syndrome (NPS) and to investigate the expressivity of open angle glaucoma (OAG) in the family members.
  
  
  METHODS
  All individuals underwent a complete ophthalmologic examination, including optical coherence tomography (OCT) of the optic disc and peripapillary region and ultrasound pachymetry. Screening for mutations in the LMX1B gene was performed by denaturing gradient gel electrophoresis and direct genomic sequencing analysis.
  
  
  RESULTS
  Ten family members had NPS, seven with varying degrees of ocular hypertension (OHT). Only one of these had advanced OAG. The others showed high pachymetry values and OCT retinal nerve fiber layer (RNFL) thickness above the normal values. Screening for mutations in the exonic and flanking sequences of the LMX1B gene showed a deletion of one G (289delG) within the coding sequence of exon 3 at codon 97, resulting in a frame shift that creates a premature stop at codon 105 (E97fsX105), predicting a truncated protein. This mutation was present in all NPS patients and absent in the unaffected family members.
  
  
  CONCLUSIONS
  A novel mutation in the homeobox transcription factor LMX1B causes NPS in a family with variable expressivity of the syndrome, including OAG. The pathogenic mechanism resulting from the mutation is presumably haploinsufficiency rather than a dominant negative effect, which would explain the clinical variability in this family. All NPS OHT patients had considerably thick corneas and RNFL.
authors.affiliation: Departamento de Oftalmología, Hospital Clínic de Barcelona, Barcelona, Spain. 28360emg@comb.es
authors.forename: Elena
authors.initials: E
authors.lastname: Millá
authors.forename: Imma
authors.initials: I
authors.lastname: Hernan
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Gamundi
authors.forename: Maria
authors.initials: M
authors.lastname: Martínez-Gimeno
authors.forename: Miguel
authors.initials: M
authors.lastname: Carballo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D018388:Codon, Terminator; D005260:Female; D016368:Frameshift Mutation; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009261:Nail-Patella Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D009798:Ocular Hypertension / Q000235:genetics; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence; D014157:Transcription Factors / Q000235:genetics*; D014463:Ultrasonography
chemical_list: D018388:Codon, Terminator; D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors