A family with six males affected by X-linked spastic paraplegia (McKusick No. 31290) is described. The disease was accompanied by mental retardation in all patients (severe in four cases with IQ of 40) and by absence of extensor pollicis longus (in four cases). The following X chromosome DNA probes were used in linkage studies: 782, RC8, 99-6, 754, OTC, L128, pDP34, p43-15, DX13, and St14. The mutation is closely linked to the loci DX13 (DXS15) and St14 (DXS52) (no recombinants in 11 meioses) and therefore localised to the telomeric region of the long arm of the human X chromosome.

Cloned coding sequences for rat and human ornithine transcarbamylase (OTC) were obtained by screening a rat and a human cDNA library respectively with a synthetic oligonucleotide corresponding to 27 bases of the rat sequence. These clones, 1100 bp long for the rat clone and 1300 bp for the human, contain approximately 80% of the human OTC coding sequence. The OTC mRNA length determined by Northern blot analysis is 1700bp. The human OTC sequence was shown to be localised Xp11.4-Xp21 using somatic cell hybrids. There is a frequent RFLP revealed with the restriction enzyme MspI. OTC is located more closely to the Duchenne muscular dystrophy mutation than previously reported markers such as RC8 and L1.28, and therefore should prove useful in carrier detection and haplotype analysis of families carrying the mutation causing the disease.