Nail patella syndrome revisited: 50 years after linkage.

Nail Patella Syndrome (NPS; OMIM #161200) is a pleiotropic condition, with a classical clinical tetrad of involvement of the nails, knees, elbows and the presence of iliac horns. Kidney disease and glaucoma are now recognised as part of the syndrome. Fifty years ago, James Renwick chose NPS to develop methods of linkage analysis in humans and revealed the third linkage group identified in man--that between NPS and the ABO blood group loci.

Phenotype severity and genetic variation at the disease locus: an investigation of nail dysplasia in the nail patella syndrome.

The genetic bases underlying the range and severity of phenotypes in Mendelian disorders is poorly understood; however, improvements in this area have the potential to facilitate analysis of oligogenic disorders. The nail dysplasia observed in Nail Patella Syndrome (NPS) was selected as a quantifiable variable within a Mendelian disorder, for which data could be readily obtained, to allow investigation of the genetic basis of variation. Analysis of SNP haplotypes across the LMX1B gene demonstrated association between the haplotype of the mutant allele and the variability in the nail score (p = 0.

A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression.

Nail patella syndrome (NPS) is an autosomal dominant disorder affecting development of the limb, kidney and eye. NPS is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. Recent studies suggest that the NPS phenotype may be more extensive than recognized previously including neurologic and neurobehavioral aspects.

The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.

LMX1B is a LIM-homeodomain transcription factor required for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Heterozygous loss-of-function mutations in LMX1B cause nail patella syndrome (NPS). To further understand LMX1B gene regulation and to identify pathogenic mutations within the coding region, a detailed analysis of LMX1B gene structure was undertaken.

Identification of TSIX, encoding an RNA antisense to human XIST, reveals differences from its murine counterpart: implications for X inactivation.

X inactivation is the mammalian method for X-chromosome dosage compensation, but some features of this developmental process vary among mammals. Such species variations provide insights into the essential components of the pathway. Tsix encodes a transcript antisense to the murine Xist transcript and is expressed in the mouse embryo only during the initial stages of X inactivation; it has been shown to play a role in imprinted X inactivation in the mouse placenta.