The underlying molecular etiology in NPS is the mutation of <i>LMX1B</i> homeobox gene which results in loss of function of its protein also called LMX1B, a DNA-binding protein belonging to the larger LIM-homeodomain transcription factor family.
Nail-patella syndrome (NPS) or hereditary onycho-osteodyaplasia is a rare genetic condition involving a mutation in the LMX1B gene affecting nails, elbows, knees, and pelvis.
Variants in the LMX1B gene cause nail-patella syndrome, a rare autosomal dominant disorder characterized by dysplasia of nails, patella and elbow abnormalities, iliac "horns," and glaucoma.
The molecular interaction between LMX1B and PAX2 has been already reported in vitro and this finding suggest that the worst renal NPS phenotype of our patient could be due to the defective expression of these two genes during nephrogenesis.
Heterozygous mutations in the gene encoding the LIM-homeodomain transcription factor (LMX1B) are identified in most patients with typical clinical findings of NPS.
Impaired transcriptional activity but not dominant negative effect of mutant LMX1B were revealed using a transcriptional reporter assay, indicating that the mutation caused nail patella syndrome in this family via haploinsufficiency of the transcriptional activity of LMX1B.
Here, we present exome sequencing and analysis of four generations of a family with a dominantly inherited Nail-Patella-like disorder (nail dysplasia with some features of Nail-Patella syndrome) who tested negative forLMX1B mutation.
Our current understanding of LMX1B function in the pathogenesis of NPS and LMX1B-associated nephropathy is also presented, and its downstream regulatory networks discussed.
Genetic and pathological analyses of additional cases would clarify the role of LMX1B in glomerulopathy without systemic symptoms, which, together with nephropathy in NPS, can be designated as 'LMX1B nephropathy'.
In this study, we identified a heterozygous microdeletion of the entire LMX1B gene using multiplex ligation-dependent probe amplification (MLPA) in a Chinese family with NPS.
Genetic and pathological analyses of additional cases would clarify the role of LMX1B in glomerulopathy without systemic symptoms, which, together with nephropathy in NPS, can be designated as 'LMX1B nephropathy'.
Mutations in LMX1B cause nail-patella syndrome, characterized by dysplasia of the patellae, nails, and elbows and FSGS with specific ultrastructural lesions of the glomerular basement membrane (GBM).
Previous studies have identified mutations in the RSPO4 and LMX1B components of the Wnt pathway in patients with the hypoplastic nail disorders anonychia and nail-patella syndrome, respectively.
Nail-Patella syndrome (NPS) is an autosomal dominant disorder that is the result of heterozygous loss-of-function mutations in LMX1B, coding for a LIM homeobox (LIM-HD) transcription factor.