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Prometaphase chromosomes from a 16 year old boy with hypogonadotrophic hypogonadism and anosmia (Kallmann syndrome) showed a tiny chromosome fragment attached to the long arm of one chromosome 1 without a visible reciprocal translocation chromosome. Chromosome painting with libraries from chromosomes 1 and X excluded a t(X;1) translocation, but failed to detect a second translocation chromosome. Through reverse chromosome painting, an unbalanced der(1), t(1;10) (q44;q26) translocation could be detected. This is the third case of Kallmann syndrome with a de novo rearrangement between two autosomes. The distal long arm of chromosome 1 may contain a candidate locus for a gene, mutations of which may cause the Kallmann phenotype; a 10q location seems less likely.

Fetal nucleated cells in the maternal circulation constitute a potential source of cells for the non-invasive prenatal diagnosis of fetal genetic abnormalities. We have investigated the use of the Magnetic Activated Cell Sorter (MACS) for enriching fetal nucleated erythrocytes. Mouse monoclonal antibodies specific for CD45 and CD32 were used to deplete leucocytes from maternal blood using MACS sorting, thus enriching for fetal nucleated erythrocytes which do not express either of these antigens. However, significant maternal contamination was present even after MACS enrichment preventing the accurate analysis of fetal cells by interphase fluorescence in situ hybridisation (FISH). To overcome this problem, we used simultaneous immunophenotyping of cells with the mouse antifetal haemoglobin antibody, UCH gamma, combined with FISH analysis using chromosome X and Y specific DNA probes. This approach enables selective FISH analysis of fetal cells within an excess of maternal cells. Furthermore, we have confirmed the potential of the method for clinical practice by a pilot prospective study of fetal sex in women referred for amniocentesis between 13 and 17 weeks of gestation.

Emery-Dreifuss muscular dystrophy (EMD) is characterised by (1) early contractures of the Achilles tendons, elbows, and postcervical muscles, (2) slowly progressive muscle wasting and weakness with a predominantly humeroperoneal distribution in the early stages, and (3) cardiomyopathy with conduction defects and risk of sudden death. Inheritance is usually X linked recessive but can be autosomal dominant. Family linkage studies have mapped X linked EMD to the distal long arm of the X chromosome but precise genetic localisation has been hampered by the rarity of this condition. We report three new families with X linked Emery-Dreifuss muscular dystrophy studied with DNA markers from Xq27-qter and three previously published families typed for additional markers. No recombination was observed with the red/green cone pigment locus, RGCP (lod score, Z = 2.46), the factor VIII coagulant gene locus, F8C (Z = 6.39), or with DXS115 (Z = 4.94). Two recombinants were observed which mapped EMD distal to DXS15 (DX13) and DXS52 (St14) respectively. Multipoint linkage analysis gave odds exceeding 200:1 for EMD being distal to these markers. A multipoint analysis incorporating published data gave the map cen-DXS304-9cM-DXS15-3cM-DXS52-2 cM-(RGCP,EMD)-3cM-F8C-2cM-DXS115 with odds of 120:1 in favour of a location for EMD between DXS52 and F8C as compared to the next best position distal to F8C.

Most of an estimated one in 504 sportswomen fail the gender verification test unjustly. Until clinical examination becomes acceptable, a new code of practice is proposed which avoids unfair disqualification.

One hundred and thirty-two Scottish families, representing the majority of currently known cases in this country with at least one living subject affected by DMD (110) or BMD (22), were studied with a series of cDNA probes excluding the 3' region of the gene (probes 10-14). Using mainly HindIII digested DNA from affected males, 89 patients showed deletions which ranged from 1 to 32 HindIII fragments in size. Two patients were also detected with exon duplications. Abnormalities were found to be particularly concentrated in the area of probe cDNA 8, with 56 patients being deleted for at least one of the fragments detected by this probe. A second smaller concentration of deletions was found with probe 1-2a which showed 16 deletions and two duplications. The endpoints of cDNA deletions or duplications were determined with a maximum variability of one HindIII fragment in 83 patients, while the remaining eight patients had a single deletion endpoint defined. The deletions found in two of our patients appear to conflict with the previously stated exon order at the 5' end of the gene. Although no specific deletion patterns were apparent for DMD, the deletions found in 13 of the BMD patients all included the most proximal (10 kb) fragment detected by probe 8.

We report on a myotonic dystrophy (DM) family exhibiting instability of normal sized (CTG)n alleles in the DM kinase gene on the non-DM chromosome. At least two mutational events involving normal DM alleles must have occurred in this family; one was characterised as a 34-35 (CTG)n repeat mutation. These findings represent a dissociation between (CTG)n repeat instability and myotonic dystrophy. Furthermore, this family highlights genetic counselling issues relating to the pathogenicity of alleles at the upper end of the normal size range and the risk of further expansion into the disease range.

Two cases of chromosomal translocations involving the long arm of chromosome 1 were investigated for 5S ribosomal gene localisation using in situ hybridisation. In the first family, there was an interstitial translocation of 1q25-32 to chromosome 5; the 5S genes remained on chromosome 1. In the second family, there was a translocation of 1q42-44 to chromosome 21q12; the 5S gene locus in this case was translocated. This shows that the 5S ribosomal genes are at position 1q42-44, confirming a previous assignment based on adenovirus-induced uncoiling and on a partial trisomy (Steffensen et al., 1977).

Cytogenetic examination of a dysmorphic infant with multiple congenital abnormalities revealed a possible de novo interstitial deletion in the long arm of chromosome 16. Conclusive proof of the deletion was obtained by flow karyotype analysis of the patient and both parents, which showed that the deleted segment was approximately 7000 kb in size.

Two families with Emery-Dreifuss muscular dystrophy (EMD) have been studied with DNA markers mapping to Xq27.3----qter. No recombination was observed in 11 phase known meioses informative for the factor VIII gene (F8C) and eight phase known meioses informative for DXS15 (DX13), giving maximum lod scores of 3.50 and 2.50 respectively at a recombination fraction of zero. DXS52 (St14) showed one recombinant in 12 phase known meioses giving a maximum lod score of 2.62 at a recombination fraction of 0.07. These results map EMD to the distal end of the long arm of the X chromosome and are an important step in the development of tests for carrier detection and prenatal diagnosis.

Pachytene quadrivalents are described in a male heterozygous for a balanced reciprocal translocation between the long arms of chromosomes 10 and 11. The break points of the translocation occur at 10q23 and 11q24. The main chromomere patterns of the bivalents correspond to the main G bands in mitosis and are sufficiently pronounced to allow the identification of bivalents 10 and 11 in normal spermatocytes.

Linkage analysis was undertaken in six families with tuberous sclerosis (TS) using a restriction fragment length polymorphism detected by v-abl. No recombinants were observed in 13 informative meioses (four phase known) giving a maximum lod score of 3.18 at zero recombination (confidence limits 0 to 0.15). This provides further evidence for the assignment of TS to 9q34 and should facilitate cloning of the structural gene, genetic counselling, and first trimester prenatal diagnosis.