We describe a 19-year-old girl with Kindler syndrome. She has suffered from bullae on pressure areas of the skin since birth. These healed with atrophic scars and caused marked atrophy of the skin of the palms and soles and wrinkled and parchment-like skin of the dorsum of the hands and feet. Since infancy the patient has also suffered from severe photosensitivity on exposed areas and developed poikiloderma on the skin of her face, neck, chest, and upper back. Since age 17 years the patient has been free of bullae but moderate photosensitivity exists. Oral examination showed limitation of mouth opening, ankyloglossia, overjet malocclusions, and atrophy of buccal mucosa with widespread white macules. Results of laboratory tests were within normal limits. The proposita's parents (family 1) are Jews of Kurdish origin and first cousins. She is the only one affected among five siblings. Family 1 is related to a second family (family 2) through a common great-grandfather. The parents of family 2 are first cousins and they have three affected children. An autosomal recessive mode of inheritance of Kindler syndrome is suggested in these two related families.

Pemphigus vulgaris in Israeli Ashkenazi and non-Ashkenazi Jews and in Austrian non-Jewish patients is strongly associated with the DR4 and DRw6 alleles of the HLA-D region class II genes. Restriction fragment length polymorphism analysis was undertaken with DQ.3, DQoa, and DRP cDNA probes. Hybridization with the DQB probe identifies Pvu II, BamHI, and EcoRV fragments that absolutely discriminate pemphigus vulgaris patients from healthy DR-, DQ-, and ethnic-matched controls. In contrast the DQa and DRB probes failed to identify disease-specific restriction fragment length polymorphism fragments. These studies indicate that DQwl and DQw3 polymorphisms carried by pemphigus vulgaris patients may be directly involved in predisposition to the disease or may be tightly linked to the susceptibility gene itself. To our knowledge, this is the first example of an HLA restriction fragment length polymorphism that is highly associated with susceptibility to autoimmune disease.Pemphigus vulgaris (PV) is a dermatological autoimmune disease mediated by autoantibodies directed against an antigen, intracellular cement substance, in the basement membrane of keratinocytes, resulting in blister formation (1, 2). This disease can be reproduced in monkeys or in mice after transfer of antibodies from PV patients (1, 2). Susceptibility to PV is strongly associated with serologically defined gene products of the HLA-D region (3, 4). technique. HLA-DR and -DQ typing was done on T-celldepleted B-cell-enriched lymphocytes by extended incubation cytotoxicity testing (7). The HLA antisera included alloantisera from the third Asia-Oceania Histocompatibility Workshop and sera of local origin.DNA Extraction, Digestion, and Binding to Nylon Membranes. Genomic DNA was extracted from peripheral leukocytes. After lysis of the erythrocytes, the leukocytes were treated with proteinase K at 0.2 mg/ml (Boehringer Mannheim) for 12 hr at 42°C. Two phenol/chloroform-isoamyl alcohol, 3:1 (vol/vol), and two isoamyl alcohol/chloroform, 1:24 (vol/vol), extractions followed. Thereafter, the DNA was precipitated with two volumes of absolute ethanol. After precipitation and several washes with ethanol, the DNA was dissolved in TE (1 mM Tris HCl/0.1 mM EDTA, pH 7.5) to give a final concentration of 1 mg/ml. Ten micrograms of each DNA sample was digested with 10 units of the following restriction enzymes: BamHI, Dra I, EcoRI, EcoRV, HincII, HindIII, Pst I, Pvu II, and Taq I. Digestion was carried out for 15 hr, and the DNA samples were subjected to electrophoresis at 30 V in agarose gel (0.7% agarose in Tris acetate buffer, pH 6.4, containing ethidium bromide at 20 ,ug/ml) for 36 hr. Gels were then transferred to Hybond N membranes (Amersham) as described by Southern (8).cDNA Probes and Hybridization. The DQa cDNA probe was furnished by Charles Auffray (College de France). The DQ,3 and DR8 cDNA probes were furnished by Hugh McDevitt and John Bell (Stanford University). Full descriptions of the probes appear elsewhere (9, 10). The probes were labeled by t...

A study of 46 patients with Alopecia areata in Jerusalem showed a significant increase in the frequency of HLA-B18 (23.9%) as compared to the control population (7.4%) with a relative risk of 3.9%. This association of HLA-B18 with AA was independent of the origin of patients, sex, age of onset and type of alopecia areata.

The Papillon-Lefèvre syndrome (PLS) is segregating in a large kindred of a Jewish isolate originating from Cochin, India. The frequency of the gene responsible for PLS among the Cochin Jews, 0.1, was estimated from the number of unrelated carriers in the isolate who married into the kindred. The obvious discrepancy between this apparently high gene frequency and the total absence of PLS in other kindreds of the isolate suggests that the syndrome may not behave as a simple autosomal recessive trait.