advertisement
Abstract #17438 Published in IGR 9-2
Novel LMX1B mutation in familial nail-patella syndrome with variable expression to open angle glaucoma
Milla E; Hernan I; Gamundi MJ; Martinez-Gimeno M; Carballo MMolecular Vision 2007; 13: 639-648
PURPOSE: 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 LMXIB 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 LMXIB 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 LMXIB 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.
Dr. E. Milla, Department of Ophthalmology, Hospital Clinic de Barcelona, Villarroel 170, 08036-Barcelona, Spain. 28360emg@comb.es
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)