Title: | Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy. |
Author(s): | Bongers, E.M.H.F. ; Huysmans, F.T.M. ; Levtchenko, E.N. ; Rooy, J.W.J. de ; Blickman, J.G. ; Admiraal, R.J.C. ; Huygen, P.L.M. ; Cruysberg, J.R.M. ; Toolens, P.A.; Prins, J.B. ; Krabbe, P.F.M. ; Borm, G.F. ; Schoots, J.; Bokhoven, J.H.L.M. van ; Remortele, A.M. van; Hoefsloot, L.H. ; Kampen, A. van ; Knoers, N.V.A.M. |
Publication year: | 2005 |
Source: | European Journal of Human Genetics, vol. 13, iss. 8, (2005), pp. 935-946 |
ISSN: | 1018-4813 |
DOI: | https://doi.org/10.1038/sj.ejhg.5201446 |
Publication type: | Article / Letter to editor |
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/47792 ![]() |
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Subject: | DCN 1: Perception and Action DCN 2: Functional Neurogenomics EBP 1: Determinants of Health and Disease EBP 2: Effective Hospital Care IGMD 3: Genomic disorders and inherited multi-system disorders IGMD 5: Health aging / healthy living IGMD 9: Renal disorder NCEBP 10: Human Movement & Fatigue NCEBP 2: Evaluation of complex medical interventions NCEBP 8: Psychological determinants of chronic illness NCMLS 5: Membrane transport and intracellular motility NCMLS 6: Genetics and epigenetic pathways of disease ONCOL 1: Hereditary cancer and cancer-related syndromes ONCOL 2: Age-related aspects of cancer ONCOL 4: Quality of Care UMCN 1.1: Functional Imaging UMCN 1.5: Interventional oncology UMCN 3.3: Neurosensory disorders UMCN 4.3: Tissue engineering and reconstructive surgery UMCN 5.4: Renal disorders EBP 1: Determinants of Health and Disease EBP 2: Effective Hospital Care NCEBP 10: Human Movement & Fatigue |
Organization: | Human Genetics Nephrology Paediatrics Radiology Otorhinolaryngology Ophthalmology Medical Psychology Health Evidence Orthopaedics |
Former Organization: | Epidemiology, Biostatistics & HTA |
Journal title: |
European Journal of Human Genetics
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Volume: | vol. 13 |
Issue: | iss. 8 |
Page start: | p. 935 |
Page end: | p. 946 |
Abstract: |
Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.
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