Nail-patella syndrome is an autosomal dominant disorder characterized by dy
plasia of finger nails, skeletal anomalies, and, frequently, renal disease.
It has recently been shown that this disorder is caused by putative loss-o
f-function mutations in a transcription factor (LMX1B) belonging to the LIM
-homeodomain family, members of which are known to be important for pattern
formation during development. A cohort of eight Dutch NPS families were sc
reened for mutations in the LMX1B gene; seven different mutations, includin
g one novel variant, were identified. Three of the mutations are very likel
y to result in truncated LMX1B proteins, three are predicted to influence s
equence-specific DNA binding, and one is presumed to prevent the formation
of a stable protein by abolishing the Zn(II) binding site of the protein. A
lthough there was a remarkable high incidence of renal disease in one of th
e families, the nephropathy was not seen in all affected family members and
the severity of renal impairment varied significantly among the patients.
This indicates that the incidence and severity of nephropathy within this f
amily cannot be attributed to the LMX1B genotype. In addition, evidence of
a correlation between other characteristics of the NPS phenotype and specif
ic mutations has not been found.