Paroxysmal Kinesigenic Choreoathetosis Locus Maps to Chromosome 16p11.2-q12.1

• Published in: American journal of human genetics 1999-12, Vol.65 (6), p.1688-1697
• Main Authors: Tomita, Hiro-aki, Nagamitsu, Shinichiro, Wakui, Keiko, Fukushima, Yoshimitsu, Yamada, Koki, Sadamatsu, Miyuki, Masui, Akira, Konishi, Tohru, Matsuishi, Toyojiro, Aihara, Masao, Shimizu, Katsunori, Hashimoto, Kiyoshi, Mineta, Mari, Matsushima, Michihito, Tsujita, Takahiro, Saito, Masaaki, Tanaka, Hajime, Tsuji, Shoji, Takagi, Toshihisa, Nakamura, Yusuke, Nanko, Shinichiro, Kato, Nobumasa, Nakane, Yoshibumi, Niikawa, Norio
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Child; Child, Preschool; Chorea - genetics; Chromosome 16p11.2-p12.1; Chromosome Mapping; Chromosomes, Human, Pair 16 - genetics; Cloning, Molecular; Convulsion; Female; Genes, Dominant - genetics; Genetic Linkage - genetics; Genetic Markers; Haplotypes - genetics; Humans; In Situ Hybridization, Fluorescence; Infant; Japan; Linkage; Male; Medical sciences; Middle Aged; Nervous system involvement in other diseases. Miscellaneous; Neurology; Paroxysmal choreoathetosis; Paroxysmal dyskinesia; Pedigree; Penetrance
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/302682

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [θ] = .00; penetrance [ p] = .7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 ( p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of ∼12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for “infantile convulsions and paroxysmal choreoathetosis” (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.