Mutations in the fibrinogen aalpha gene account for the majority of cases of congenital afibrinogenemia.

Congenital afibrinogenemia is a rare, autosomal, recessive disorder characterized by the complete absence of detectable fibrinogen. We previously identified the first causative mutations in a nonconsanguineous Swiss family; the 4 affected persons have homozygous deletions of approximately 11 kb of the fibrinogen alpha (FGA) gene. Haplotype data implied that these deletions occurred on distinct ancestral chromosomes, suggesting that this region may be susceptible to deletion by a common mechanism. We subsequently showed that all the deletions were identical to the base pair and probably resulted from a nonhomologous recombination mediated by 7-bp direct repeats. In this study, we have collected data on 13 additional unrelated patients to identify the causative mutations and to determine the prevalence of the 11-kb deletion. A common recurrent mutation, at the donor splice site of FGA intron 4 (IVS4 + 1 G > T), accounted for 14 of the 26 (54%) alleles. One patient was heterozygous for the previously identified deletion. Three more frameshift mutations, 2 nonsense mutations, and a second splice site mutation were also identified. Consequently, 86% of afibrinogenemia alleles analyzed to date have truncating mutations of FGA, though mutations in all 3 fibrinogen genes, FGG, FGA, and FGB, might be predicted to cause congenital afibrinogenemia.

Transthyretin gene analysis in European patients with suspected familial amyloid polyneuropathy.

We investigated 99 patients from 64 European families (51 French, 11 British, one Italian and one Spanish) with suspected familial amyloid polyneuropathy (FAP) for transthyretin (TTR) gene mutations. Thirty-nine families were found to have point mutations causing the following amino acid substitutions: Met30 (28 families), Tyr77 (five), Arg 50 (one), Ala49 (one), Gln89 (one), Ala60 (one) and one each with previously undescribed mutations at Asn35 and Gys54. The clinical picture in the patients with new and known mutations were typical of FAP, without any specific features for a particular mutation. Onset of symptoms was late (over 50 years) in many French and British patients with the Met30 and Tyr77 mutations, and only 30% of all index cases had affected relatives. We propose an approach to molecular diagnosis in European patients with FAP, apart from members of families with known mutations, based on the frequency of TTR mutations observed in this and and other studies of FAP in Europe. It is logical to screen for the Met30 and Tyr77 mutations and Ala60 in the UK, using restriction enzyme analysis. If these are absent, the TTR gene should be sequenced directly to detect less common or unknown mutations.

[Original technic for preoperative hemodilution permitting deferred autologous transfusion (apropos of 106 cases)]. / Technique originale d'hémodilution préopératoire permettant la transfusion autologue différée (à propos de 106 cas).

To carry out normovolemic haemodilution in the best security conditions we elaborate a new method of preoperative haemodilution. Collection of red cell concentrates and adequate compensation are made either in the blood bank or at the patient's bed side. There are two ways of proceeding: *manual plasmapheresis technic is used for the collection of less than 450 ml packed red cells; *collection of more than 450 ml packed red cells is carried out on a PCS Haemonetics cell separator. CPD autologous red cells concentrates prepared in that way can be stored to meet the patient's need during and after the operation. The patient is identified as donor and receiver as regards laboratory analysis and computer treatment as well. Information's transmission between blood bank hospital and clinics is secured with the same document. This method enables homologues transfusion save and completes autologous transfusion in 68% cases among 106 patients. It is to be noticed that none of the 98 haemodiluted patients suffered from thrombosis.