No abstract

Two subjects, of 11,000 healthy individuals screened, were found to be missing three and four immunoglobulin isotypes, respectively (IgAl, IgG2, and IgG4; IgAl, IgG2, IgG4, and IgE), and have beei analyzed at the DNA level by means of Southern blotting and Ig heavy-chain-specific probes. A broad deletion within the heavy-chain constant region (C) gene cluster was found on chromosome 14 of both probands. Two different haplotypes are described: the first has lost the Cai,, Cty, Cy2, Cy4, and CE genes; the second lacks the Cp,> Ca., Cy,1 C.,2, andhCy4 genes. These findings confirm the reciprocal order of the Ig heavy-chain genes as derived by molecular cloning. The inclusion of the C*, gene within the deleted regions confirms its location between Ca, and Cy2.From the observed frequency of the homozygous genotype, 1%-3% of healthy subjects from our population are expected to be heterozygous for multiple heavy-chain gene deletions. Cross-over between mispaired homologous regions seems to be the favored mechanism of multiple Ig gene deletions and duplications, and, generally, in the evolution of the human Ig heavy-chain gene family.

No abstract

Twenty-seven Bence Jones proteins of immunological type K show a common set of peptides. One 6f the commnon peptides differs in three of the proteins which are the only ones classified by a serological test as Iav(a+). The difference in the peptide analyzed is caused by a valine-leucine interchange; Inv(a+) proteins have leucine, whereas Inv(a-) proteins have valine in position 189.

Immunoglobulin (Ig) allotype typing is usually performed with serological methods based on hemagglutination inhibition. The recent development of molecular techniques has allowed the molecular typing of several Ig markers. The hinge, CH2, and CH3 domains of the G2 gene from six unrelated individuals (three G2m(n+) and three G2m(n-)) were amplified and cloned to establish the molecular basis of the G2mn+ and G2mn- . Comparison of the allele sequences revealed three changes: two (codons 308 and 437) are silent exonic substitutions, one is a G to A transition corresponding to an amino acid difference in position 282: Val (GTG) in G2mn- , Met (ATG) in G2mn+ . These substitutions were identified via two approaches: 282 polymorphism, after digestion of a specific polymerase chain reaction product with Nla III followed by acrylamide electrophoresis; 308 and 437, by a dot-blot technique using allele-specific oligonucleotides. These molecular typing results correspond exactly to those obtained serologically; moreover, the three substitutions defining the G2mn+ and G2mn- alleles are always associated in a strict linkage disequilibrium.

A B S T R A C T Immunohistological and elution

Six cases of cystic hygromas detected during second trimester ultrasound examination are reported: 4 fetuses (67 per cent) had a 45, X karyotype, 1 fetus had trisomy 18, 1 fetus had a normal karyotype (46,XX) and at autopsy multiple anomalies were observed. In the latter case the family history suggested an autosomal recessive pattern of inheritance. In order to reach a definite diagnosis and give proper genetic counselling when a fetus is found to have cystic hygroma, a fetal karyotype as well as a family and reproductive history should be obtained.

SUMMARY The association of HLA-A,B,C, DR polymorphisms and of Bf and GLO with coeliac disease was analysed in 100 Italian children. Primary involvement of HLA-DR3 and DR7 is apparent, while specificities of nearby loci are probably associated secondarily, because of linkage disequilibrium. Direct assessment of D/DR genotype through family studies and mixed lymphocyte cultures led to the recognition of two high risk genotypes DR3/3 and DR3/7, and of two lower risk genotypes DR3/X and DR7/X. The different weight of the HLA-dependent genetic factors is to some extent correlated with the clinical and immunological parameters, suggesting that the low-risk genotypes induce a milder expression of coeliac disease. Furthermore, other genetic factors, such as sex, appear to contribute to the penetrance of the disease, especially in the case of DR3/X and DR7/X. Both genetic and environmental factors contribute to the onset and to clinical progression of coeliac disease. The role of genetic factors has long been substantiated by a high concordance rate in monozygotic twins, and an increased incidence of overt malabsorption or of asymptomatic histological lesions in first-degree relatives.' 2 More recently, the association between markers of the HLA system and coeliac disease has provided new evidence of the importance of genetic factors in this disease. 8 Different genetic models have been put forward, which propose dominant or recessive expression of HLA-linked gene(s), or in addition assume the involvement of non-HLA gene(s).9 I() In susceptible individuals, exposure to dietary gluten, or to purified gliadin fractions under experimental conditions, is the leading known environmental factor. Clinical and/or histological improvement on a gluten-free diet and relapse after gluten challenge have thus been established as fixed diagnostic criteria.11 Nevertheless, the protean nature of the clinical picture is adequately shown by the significant proportion of atypical cases.'2 As part of an ongoing study, the present report (1) provides further evidence of the association of