Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a potentially fatal hypermetabolic crisis triggered by commonly used anaesthetic agents. The demonstration of genetic heterogeneity in MHS prompted the investigation of the roles played by calcium regulatory proteins other than the ryanodine receptor (RYR1), which is known to be linked to MHS in fewer than half of the European MHS families studied to date. Previously, we have excluded the genes encoding the skeletal muscle L-type voltage-dependent calcium channel alpha 1-, beta 1- and gamma-subunits as candidates for MHS. In this report, we describe the cloning and partial DNA sequence analysis of the gene encoding the alpha 2/delta-subunits, CACNL2A, and its localization on the proximal long arm of chromosome 7q. A new dinucleotide repeat marker close to CACNL2A was identified at the D7S849 locus and tested for linkage in six MHS families. D7S849 and flanking genetic markers were found to co-segregate with the MHS locus through 11 meioses in one, three-generation family. These results suggest that mutations in or near CACNL2A may be involved in some forms of this heterogeneous disorder.

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The flow karyotype of rat chromosomes was determined by dual beam flow cytometry. Eighteen fractions were sorted and subsequently amplified by degenerate oligonucleotide primed-PCR as described by Telenius et al. (1992a, 1992b). The PCR products were labeled and used as probes for fluorescence in situ hybridization on rat fibroblast metaphases. The amplified chromosomes were detectable as bright chromosome paints and in most cases the signal was evenly distributed along the whole chromosome except for the centromeric region in half of the chromosomes. The results show that chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 19, 20, X and Y can be sorted as individual fractions, whereas chromosomes 11, 13, 14,15 and chromosomes 16, 17 and 18 are clustered together in the flow karyotype.

A balanced complex chromosome rearrangement (CCR) involving four chromosomes is very rare and may lead to different types of aneuploid germ cells. We report a liveborn child with multiple congenital anomalies and an apparently balanced translocation, t(11;12). High resolution chromosome analysis in the mother showed a CCR involving chromosomes 5, 11, 12, and 16. In situ hybridisation showed that this CCR was the result of a five break rearrangement, and that the derivative chromosome 12 consisted of parts of chromosomes 5, 11, and 12. From this it could be deduced that the karyotype of the child was not balanced, but resulted in partial trisomy for Sq and partial monosomy for 12p. The clinical findings in the child were compatible with partial trisomy for 5q.

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