TY - JOUR
T1 - Parkin gene modifies the effect of RLS4 on the age at onset of restless legs syndrome (RLS)
AU - Pichler, Irene
AU - Marroni, Fabio
AU - Pattaro, Cristian
AU - Lohmann, Katja
AU - De Grandi, Alessandro
AU - Klein, Christine
AU - Hicks, Andrew A.
AU - Pramstaller, Peter P.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - A co-occurrence of restless legs syndrome (RLS) and Parkin mutations has been described. In South Tyrolean RLS patients, a novel RLS locus has been found (RLS4) and recurrent Parkin mutations have been reported. By a systematic screen we investigated the presence of founder Parkin mutations in South Tyrolean RLS patients with known carrier status at the RLS4 locus and assessed whether these mutations alone or in combination influence the RLS phenotype measured by three quantitative RLS traits (age at onset (AAO) and two severity measurements). The Parkin mutation alone showed no effect, whereas RLS4 had a significant effect on the AAO (P=0.0096, decrease of AAO of 9.1 years), but did not influence severity. Carriers of both, a Parkin mutation and the RLS4 haplotype, showed an association with AAO (P=0.0016), corresponding to an anticipation of RLS onset age of 16.9 years. However, there was no effect on the disease severity. Our results suggest that the occurrence of a heterozygous Parkin mutation works in tandem with the gene at the RLS4 locus to lower the AAO in RLS.
AB - A co-occurrence of restless legs syndrome (RLS) and Parkin mutations has been described. In South Tyrolean RLS patients, a novel RLS locus has been found (RLS4) and recurrent Parkin mutations have been reported. By a systematic screen we investigated the presence of founder Parkin mutations in South Tyrolean RLS patients with known carrier status at the RLS4 locus and assessed whether these mutations alone or in combination influence the RLS phenotype measured by three quantitative RLS traits (age at onset (AAO) and two severity measurements). The Parkin mutation alone showed no effect, whereas RLS4 had a significant effect on the AAO (P=0.0096, decrease of AAO of 9.1 years), but did not influence severity. Carriers of both, a Parkin mutation and the RLS4 haplotype, showed an association with AAO (P=0.0016), corresponding to an anticipation of RLS onset age of 16.9 years. However, there was no effect on the disease severity. Our results suggest that the occurrence of a heterozygous Parkin mutation works in tandem with the gene at the RLS4 locus to lower the AAO in RLS.
UR - http://www.scopus.com/inward/record.url?scp=73949124762&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.30988
DO - 10.1002/ajmg.b.30988
M3 - Journal articles
C2 - 19526454
AN - SCOPUS:73949124762
SN - 1552-4841
VL - 153
SP - 350
EP - 355
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 1
ER -