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Summary Using a highly discriminatory DNA typing technique, based on the polymerase chain reaction and reverse dot blot hybridization, more refined results were obtained on the association of particular HLA class II alleles, haplotypes and genotypes with insulin-dependent diabetes mellitus in the Belgian population. The previously reported predisposing effect for the DRBI*0301 encoded DR3 serologic specificity was confirmed and could be assigned to the DRB3*0200 encoded DR52b serologic specificity. A second high risk haplotype, DRBI*0401-DQBI*0302 encoding the DR4-DQ8 serologic specificity, accounted for increased susceptibility both in the total insulin-dependent diabetic population and among DR4-positive patients. Moreover, we found that these DR4 associated DRB1 and DQB1 alleles act as independent risk factors. A possible role for the DPB1 locus can be rejected since the observed predisposing effect for DPBI*0202 probably occurred due to linkage disequilibrium of this allele with DRBI*0301. Particular extended haplotypes accounted for the decreased relative risk observed for the DR2, DR11 and DR13 serologic specificities. The highest relative risk was observed for those DQA1/DQB1 genotypes, allowing for the formation of 4SS (DQ0~Arg52+/DQflAsp57-) heterodimers. [Diabetologia (1994) 37: 808-817] Key words Insulin-dependent diabetes mellitus, HLA, class II, PCR, SSO typing.IDDM results from the autoimmune destruction of the pancreatic insulin-producing beta cells. Concordance rates for monozygotic twins (36 %), HLA-identical and -haplo-identical siblings (13 % and 4.5 %, respectively) suggest a multifactorial predisposition for this disease, the genetic factor being only partly determined by the HLA genes [1,2].

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Nonspecific X‐linked mental retardation (XLMR) is a common disorder. The number of genes involved in this condition is not known, but it is estimated to be more than 10. We present a clinical and linkage study on 3 families with XLMR. All families were analyzed using highly polymorphic markers covering the X chromosome; screening for the fragile X mutation was negative. The first family (MRX 36) consisted of 1 female and 4 male patients in 3 generations and 7 healthy individuals. Considering the female as an expressing heterozygous carrier, a maximum LOD score of 3.41 was reached in region Xp21.2–Xp22.1. Considering her phenotype to be unknown, a LODmax of 1.97 was reached in the same region. The second family consisted of 5 affected and 6 healthy males with mild to borderline mental retardation. Linkage analysis using an X‐linked recessive model with full penetrance and no phenocopies excluded linkage over almost the entire X chromosome. Using alternative models, including an affecteds‐only analysis, a LODmax of 1.49 was found in region Xq24–28. The third family, consisting of 4 male patients with moderate mental retardation in 1 generation yielded a LODmax of 0.9 in region Xp22.13–11.3. However, even in this small pedigree, exclusion mapping was able to exclude very large parts of the X chromosome and in this way identify a likely candidate region. © 1996 Wiley‐Liss, Inc.