Paroxysmal kinesigenic choreoathetosis (PKC): confirmation of linkage to 16p11-q21, but unsuccessful detection of mutations among 157 genes at the PKC-critical region in seven PKC families.
Paroxysmal kinesigenic choreoathetosis (PKC) is a paroxysmal movement disorder of unknown cause. Although the PKC-critical region (PKCCR) has been assigned to the pericentromeric region of chromosome 16 by several studies of families from various ethnic backgrounds, the causative gene has not yet been identified. In the present study, we performed linkage and haplotype analysis in four new families with PKC, as well as an intensive polymerase chain reaction (PCR) based mutation analysis in seven families for a total of 1,563 exons from 157 genes mapped around the PKCCR. Consequently, the linkage/haplotype analysis revealed that PKC was assigned to a 24-cM segment between D16S3131 and D16S408, the result confirming the previously defined PKCCR, but being unable to narrow it down. Although the mutation analysis of the 157 genes was unsuccessful at identifying any mutations that were shared by patients from the seven families, two nonsynonymous substitutions, i.e., 6186C>A in exon 3 of SCNN1G and 45842A>G in exon 29 of ITGAL, which were segregated with the disease in Families C and F, respectively, were not observed in more than 400 normal controls. Thus, one of the two genes, SCNN1G and ITGAL, could be causative for PKC, but we were not able to find any other mutations that explain the PKC phenotype.
Kikuchi
Taeko
T
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.|Department of Psychiatry, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Solution Oriented Research of Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, Japan.
Nomura
Masayo
M
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.|Solution Oriented Research of Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, Japan.
Tomita
Hiroaki
H
Department of Psychobiology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Harada
Naoki
N
Kyushu Medical Science, Nagasaki, Japan.|Solution Oriented Research of Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, Japan.
Kanai
Kazuaki
K
Department of Neurology, Chiba University School of Medicine, Chiba, Japan.
Konishi
Tohru
T
Division of Pediatrics, Nagaoka Ryoikuen, Nagaoka, Japan.
Yasuda
Ayako
A
Department of Pediatrics, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
Matsuura
Masato
M
Section of Biofunctional Informatics, Graduate School of Allied Health Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Kato
Nobumasa
N
Department of Psychiatry, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Yoshiura
Koh-Ichiro
KI
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan. kyoshi@nagasaki-u.ac.jp.|Solution Oriented Research of Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, Japan. kyoshi@nagasaki-u.ac.jp.
Niikawa
Norio
N
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.|Solution Oriented Research of Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, Japan.
D001264:Athetosis / Q000235:genetics*; D002819:Chorea / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D010375:Pedigree