Mutational analysis of neurotensin in familial restless legs syndrome.
A susceptibility locus for restless legs syndrome (RLS) has been identified recently on chromosome 12q. This region contains several transcribed genes including neurotensin (NTS), which, as an important modulator of the dopaminergic transmission, represents a strong functional and positional candidate in the context of RLS. In this study, NTS was evaluated for mutational analysis. A panel of 19 individuals from 4 families supporting linkage to 12q was investigated using a combined denaturing high-performance liquid chromatography (dHPLC) and direct sequencing method. Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5' untranslated region (UTR). None of the observed variants co-segregated with RLS and no disease-associated polymorphisms were detected in any of the analyzed families. Based on these results, it is unlikely that NTS is the gene responsible for RLS in chromosome 12-linked families.
Desautels
Alex
A
Centre d'étude du sommeil, Hôpital du Sacré-Coeur de Montréal and Centre de recherche en sciences neurologiques, Université de Montréal, Québec, Canada.
Turecki
Gustavo
G
Xiong
Lan
L
Rochefort
Daniel
D
Montplaisir
Jacques
J
Rouleau
Guy A
GA
D020121:5' Untranslated Regions / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D009496:Neurotensin / Q000235:genetics*; D010292:Paresthesia / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012148:Restless Legs Syndrome / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA
D020121:5' Untranslated Regions; D009496:Neurotensin