The 1396del A mutation and a missense mutation or a rare polymorphism of the WRN gene detected in a French Werner family with a severe phenotype and a case of an unusual vulvar cancer. Mutations in brief no. 136. Online.

The Werner's syndrome (WS) is a rare recessive disease characterized by an early onset of geriatric disorders. The Werner's syndrome gene (WRN) recently cloned, encodes for an helicase and therefore plays a role in DNA metabolism and DNA repair. Here, we report the study of a French family with two affected members and numerous cancers. Using the protein truncation test and sequencing, we identified a homozygous mutation in the WRN gene. This mutation generates a frame shift leading to a very short 391 amino acids truncated protein without the helicase motif. A particularly severe phenotype of the affected patient was associated with an unusual vulvar cancer traditionaly observed in elderly patients and therefore likely to be related to the Werner's syndrome. An additional substitution of G for A at nucleotidic position 1392 was also described. We suggest that a relation between genotype and phenotype could exist in the studied family.

Human monoclonal antibodies against blood group antigens. Preparation of a series of stable EBV immortalized B clones producing high levels of antibody of different isotypes and specificities.

The EBV immortalization technique was used to produce stable clones, from B lymphocytes, secreting human monoclonal antibodies to Rh(D), Rh(G), Rh(c), Rh(E), Kell, A and A1 blood group antigens. These clones were obtained from peripheral blood lymphocytes of hyperimmunized plasmapheresis donors or from spleen lymphocytes of immunized patients. Mean levels of antibody concentration varied between 4 and 50 micrograms/ml. The antibodies obtained were of IgG1, IgG2, IgM or IgA class. Most of the clones have been stable for growth and antibody production during long periods of continuous culture, extending upto 4 years. Hybridization of two clones was effected with the human lymphoblastoid cell line KR-4 and with the mouse myeloma X63-Ag8.653, but did not result in any marked improvement of clone characteristics. One of the anti-Rh(D)-producing EBV-transformed clones was used to produce an anti-Rh(D) typing reagent which has proved satisfactory for 2 years in routine blood typing in several laboratories.

[Diagnostic and therapeutic use of human anti-D (Rho) monoclonal antibodies. Evaluation and perspectives]. / Utilisation diagnostique et thérapeutique d'anticorps monoclonaux humains anti-D (Rho). Bilan et perspectives.

Human monoclonal antibodies will be essential in medicine. They are valuable tools for biological diagnosis and therapeutics. Our model, human monoclonal antibodies directed against the Rhesus D antigen can be used for the determination of the Rhesus D phenotype and for the suppression of Rh(D) immunisation in women. These new products require new procedures of preparation, new regulations for the quality controls, which will be discussed in this paper.