Genetic Mapping of the Camurati-Engelmann Disease Locus to Chromosome 19q13.1-q13.3

Camurati-Engelmann disease (CED [MIM 131300]), or progressive diaphyseal dysplasia, is an autosomal dominant sclerosing bone dysplasia characterized by progressive bone formation along the periosteal and endosteal surfaces at the diaphyseal and metaphyseal regions of long bones and cranial hyperostosis, particularly at the skull base. The gene for CED, or its chromosomal localization, has not yet been identified. We performed a genomewide linkage analysis of two unrelated Japanese families with CED, in which a total of 27 members were available for this study; 16 of them were affected with the disease. Two-point linkage analysis revealed a maximum LOD score of 7.41 (recombination fraction .00; penetrance 1.00) for the D19S918 microsatellite marker locus. Haplotype analysis revealed that all the affected individuals shared a common haplotype observed, in each family, between D19S881 and D19S606, at chromosome 19q13.1-q13.3. These findings, together with a genetic distance among the marker loci, indicate that the CED locus can be assigned to a 15.1-cM segment between D19S881 and D19S606

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

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