BACKGROUND: Restless legs syndrome (RLS) is a common sensory-motor disorder 
characterized by paresthesias and an intense urge to move the legs with a 
considerable familial aggregation. To date, no gene mutation has been found, but 
five gene loci have been mapped in primary RLS to chromosomes 12q, 14q, 9p, 2q, 
and 20p (RLS1 through 5).
PATIENTS/METHODS: We identified a four-generational German RLS family with 37 
family members including 15 affected cases. We performed linkage analysis using 
microsatellite markers at the five known loci. Prompted by the identification of 
a potentially shared haplotype near the RLS3 locus, we expanded the investigated 
linkage region on chromosome 9p using additional DNA markers.
RESULTS: Mode of inheritance in our RLS family was compatible with an autosomal 
dominant pattern, and disease onset was mainly in childhood or adolescence. We 
excluded linkage to the RLS1, RLS2, RLS4, and RLS5 loci. However, we identified 
a likely new RLS gene locus (RLS3*) on chromosome 9p with a maximum lod score of 
3.60 generated by model-based multipoint linkage analysis. A haplotype flanked 
by D9S974 and D9S1118 in a 9.9-Mb region, centromeric to RLS3, was shared by all 
12 investigated patients. In addition, 11 of them carried a common haplotype 
extending telomeric to D9S2189 that is located within RLS3.
CONCLUSIONS: We demonstrate linkage to a locus on chromosome 9p that is probably 
distinct from RLS3. Our family with a rather homogeneous phenotype and very 
early disease onset represents a unique opportunity to further elucidate the 
genetic causes of the frequent restless leg syndrome.