Since the loci for the ABO blood group (ABO), nail-patella syndrome (Np), and AK1 are known to be linked in man, the ABO:Np:AK1 linkage group may be assigned to chromosome 9.
In addition, these studies place COL5A1 near the locus for the genetic disorder, nail-patella syndrome (hereditary osteo-onychodysplasia), which also maps to 9q34.
We have employed 3'-untranslated region RFLPs to exclude COL5A1 as a candidate gene in families with tuberous sclerosis 1, Ehlers-Danlos syndrome type II, and nail-patella syndrome.
Recombinations were detected, by two-point linkage analysis, between NPS and the centromeric markers D9S60 and the gelsolin gene and the telomeric markers D9S64 and D9S66, in one of the families.
These findings help to explain the high degree of variability in the NPS phenotype, and suggest that the skeletal defects in NPS are a result of the diminished dorsoventral patterning activity of LMX1B protein during limb development.
Our results demonstrate an essential function for Lmx1b in mouse limb and kidney development and suggest that NPS might result from mutations in the human LMX1B gene.
Our results demonstrate an essential function for Lmx1b in mouse limb and kidney development and suggest that NPS might result from mutations in the human LMX1B gene.
Recently, LMX1B , a transcription factor of the LIM-homeodomain type with homologs that are important for limb development in vertebrates, was mapped to the same general location as NPS at 9q34.
Mouse Lmx1b maps to a region syntenic to that of the NPS gene, and kidneys of Lmx1b mutant mice exhibit pathological changes similar to that observed in NPS (refs 5,6).
By using FISH with probes from 9q the breakpoint region was narrowed to a 17.0 cM interval between D9S262 and ABL, which includes the NPS critical region.