We report that mutation in the gene for plectin, a cytoskeleton-membrane anchorage protein, is a cause of autosomal recessive muscular dystrophy associated with skin blistering (epidermolysis bullosa simplex). The evidence comes from absence of plectin by antibody staining in affected individuals from four families, supportive genetic analysis (localization of the human plectin gene to chromosome 8q24.13-qter and evidence for disease segregation with markers in this region) and finally the identification of a homozygous frameshift mutation detected in plectin cDNA. Absence of the large multifunctional cytoskeleton protein plectin can simultaneously account for structural failure in both muscle and skin.

The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders combining defects of craniofacial and limb development. The predominantly preaxial form is called Nager AFD, the predominantly postaxial form of AFD (POADS) is also known as the Genée-Wiedemann or Miller syndrome. The former appears to be about twice as common as the latter with well-documented autosomal dominant and recessive occurrences in both conditions. Only 1 AD occurrence of POADS is known, but 5 sets of sibs are suggestive of AR inheritance. Heterogeneity of apparently nonsyndromal AFD of both types is powerful support for the hypothesis that the AFDs are polytopic field defects arising during blastogenesis. Six other previously described forms of AFD include the AFD syndrome of Kelly et al. (AR), the Rodríguez or Madrid form of AFD (AR or XLR), the Reynolds or Idaho form of AFD (AD), the Arens or Tel Aviv type of AFD (AF?), the presumed AR AFD syndrome of Richieri-Costa et al., and the AD Patterson-Stevenson-Fontaine syndrome. Here we review the AFDs and report on a previously apparently undescribed autosomal or X-linked dominant form of AFD with mental retardation in a Sicilian mother and her 4 sons.

The aim of the present study was to verify the analytical performances of high-performance liquid chromatography (HPLC) and micellar electrokinetic capillary chromatography (MEKC) for the separation and qualitative determination of a selected group of organic components of smokeless gunpowders. The HPLC method was based on a gradient reversed-phase elution with a mobile phase composed of 0.17 M H(3)PO(4)/methanol; detection was performed by UV absorption at the wavelengths of 220, 254, and 270 nm. The MEKC experiments were carried out by using uncoated fused-silica capillaries (50 microm inside diameter, 50 cm effective length) and a running buffer composed of 10 mM sodium tetraborate at pH 9.24 added with 25 mM sodium dodecyl sulfate (SDS); the applied voltage was 25 kV; detection was either at a fixed wavelength UV of 214 nm or with a diode-array detector operating in the wavelength range from 190 to 350 nm. Both reversed-phase HPLC and MEKC techniques succeeded in resolving the tested standard mixtures of organic components of smokeless powders. Although the sequence of elution of the different analytes was slightly different between HPLC and MEKC, a statistical analysis based on the Spearman's rank correlation test showed that the two separation patterns were highly correlated. HPLC and MEKC were comparable in terms of elution/migration time precision, whereas MEKC showed higher reproducibility of peak areas. The interfacing of capillary electrophoresis with diode array UV detection provided distinct UV spectra of the individual analytes, thus improving, on the detection side, the analytical selectivity and identification power of capillary electrophoresis.

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To strengthen the evidence for genetic linkage to COL7A1, we have studied 26 generalised recessive dystrophic epidermolysis bullosa (EB) families of British, Italian, Irish, and South African origin. We chose two linkage markers, a COL7A1 PvuII intragenic polymorphism and a highly informative anonymous microsatellite marker, D3S1100, which maps close to the COL7A1 locus at 3p21.1-3. Diagnosis was established by family history, clinical examination, immunofluorescence, and ultrastructural studies. The PvuII marker was informative in 16 families with a maximum lod score (Zmax) of 3 51 at recombination fraction (0) = 0. The D3S11OO microsatellite was informative in 24 out of 25 families with Zmax=6*8 at 0=0-05 (Z=4-94 at 0=0) and no obligatory recombination events. These data strongly suggest that COL7A1 mutations cause EB in these families and, combined with previous studies, indicate locus homogeneity. The importance ofanchoring fibrils for dermal-epidermal adhesion is further underlined. D3S11OO may later prove useful in prenatal diagnosis of this disease, if used in combination with other markers. (J Med Genet 1994;31:745-748) Epidermolysis bullosa (EB) encompasses a group of inherited diseases characterised by inappropriate blistering of the skin after minor trauma. Clinically it varies from a limited, nonscarring form to a severe mutilating disorder with widespread loss ofskin and scarring. Three major types are separated on the basis of the microscopic level of blistering within the skin': (1) EB simplex with cleavage through the basal epidermis; (2) junctional EB with cleavage through the lamina lucida of the basement membrane; and (3) dystrophic EB with cleavage below the lamina densa of the basement membrane. Dystrophic EB has autosomal dominant and recessive forms. Attempts at further sub-categorisation2 have been based on both clinical and microscopic variation in the phenotype, but there is overlap between categories causing difficulties in precise classification.COL7A1 is the prime candidate gene for both autosomal dominant and recessive dystrophic EB. Anchoring fibrils, visible on electron microscopy as cross banded fanning structures extending from the lower lamina densa into the papillary dermis, are composed mainly of type VII collagen3 and have both qualitative and quantitive abnormalities in dystrophic EB.45 In generalised recessive dystrophic EB, recognisable anchoring fibrils may be missing and immunofluorescence staining with type VII collagen antibodies is markedly reduced or absent.8 Partial cloning of COL7A19 and identification of an intragenic PvuII polymorphism'0 enabled demonstration of tight linkage to dominant dystrophic EB"1'3 and, in one study of 19 patients from France, to generalised recessive dystrophic EB with Zmax = 3 97 at 0 =o.l4 Recently a homozygous insertion-deletion within the N-terminal noncollagenous (NC1) domain of COL7A1 has been recognised in a generalised recessive dystrophic EB patient'5 and a methionine to lysine substitution within the C-terminal non-c...