This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Nail Patella Syndrome (NPS) is a pleiotropic autosomal dominant condition affecting the nails, skeletal system, kidneys and eyes. Skeletal features include absent or hypoplastic patellae, patella dislocations, elbow abnormalities, talipes and iliac horns. Kidney involvement may lead to renal failure and there is also a risk of glaucoma. Heterozygous loss of function mutations in the gene encoding the transcription factor LMX1B cause NPS in humans. Evidence from animal models suggest that loss of LMX1B function affects the dorso-ventral polarity of the developing limb, resulting in nail dysplasia, patellar hypoplasia and the aberrant muscle insertions observed among NPS patients. Because LMX1B is a transcription factor, some NPS disease manifestations are also due to abnormal downstream regulation of other transacting genes; this is evidenced by LMX1B's influence on COL4A4 expression in glomerular basement membrane. As progress is made to understand LMX1B's function at a molecular and cellular level, it is imperative that affected individuals are accurately phenotyped in order to understand the manifestations of LMX1B mutations at an organism level. This will allow earlier detection, intervention and, possibly treatment and prognosis of the disease components of NPS. Provisions to collect longitudinal clinical data from this NPS study cohort will also provide information about the progression of kidney disease that can then be applied to all NPS patients.
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