SUMMARY Monozygotic twin girls are reported, one of whom has the typical clinical features of Duchenne muscular dystrophy despite a normal female karyotype. Although certain features of the biopsy were atypical, the clinical diagnosis was supported by persistent markedly raised blood creatine kinase levels and findings typical of DMD on electromyography and magnetic resonance spectroscopy.Analysis of an X linked DNA polymorphism in 16 independent somatic cell hybrids made between cells derived from each girl and a mouse line suggest that in one twin only the maternal X chromosome is active, whereas in the other the active X was paternally derived. More data are needed to exclude sampling error. These preliminary experimental results support the hypothesis that both girls are heterozygous for Duchenne muscular dystrophy. X inactivation, by chance, resulted in two contrasting cell masses with different active X chromosomes. This segregation was followed by, and may even have resulted in, twinning into a female pair, one normal and one with the full clinical features of the disease.In 1977 Gomez et al' reported pseudohypertrophic muscular dystrophy in one of monozygotic twin girls. In 1982 Pena et al2 published an abstract giving details of a similar family. In both families there was a history of Duchenne muscular dystrophy. In the first report the unaffected twin had a raised serum creatine kinase level. In the second the clinically normal monozygotic twin sister of the proband gave birth to an affected son. These observations support the contention that such cases arise as a result of an unusual pattern of X chromosome inactivation producing one female in whom nearly all cells expressed the X chromosome with the Duchenne gene.We report a further case of Duchenne-like, rapidly progressive, pseudohypertrophic muscular dystrophy in one of monozygotic twin girls and extend the hypothesis to suggest that the segregation of cells on the basis of X inactivation might actually have caused monozygotic twinning. Preliminary studies to identify the active X chromosome in the two girls using mouse-human hybrids are presentefi.Received for publication 23 May 1986. Rcvised version accepted for publication 25 July 1986. These support the hypothesis and make it likely that I the twin pair will be of considerable value in the search for the genetic and cellular basis of Duchenne muscular dystrophy.

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Abstract. Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liverenriched transcription factors. C/EBP' LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNFI and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher.

We have assembled a panel of monochromosomal somatic cell hybrids for use in gene mapping. DNA from each individual hybrid was used as a probe on normal human metaphases to identify the human chromosome and any fragments by reverse painting. To test the efficiency of the panel PCR amplification of DNA from the monochromosomal somatic cell hybrid panel was used in combination with human specific oligonucleotide primers to assign alpha-catenin (CTNNA1) and p21/WAF1 to chromosomes 5 and 6 respectively. These genes were localized further using hybrids containing specific translocations to 5q11-qter and 6p21 respectively. We also developed primers to enable us to assign 17 ESTs sequenced by the HGMP Resource Centre. The hybrid panel was developed with support of the UK HGMP and the DNA is available to all registered users.