Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A.

To provide a National database, 1,410 unrelated hemophilia A (HA) patients were investigated using screening methods denaturing high-performance liquid chromatography (DHPLC), conformational-sensitive gel electrophoresis (CSGE)] and/or direct sequencing. F8 gene mutations were identified in 877 (81%), 146 (82%), and 133 (89%) families with severe, moderate, or mild HA, respectively. Among the 382 different mutations detected, 217 (57%) have not previously been reported in the F8 Haemophilia A Mutation, Structure, Test and Resource Site (HAMSTeRS) database. Mutations leading to a null allele accounted for 82, 15%, and less than 1% of severe, moderate, or mild HA, respectively. A missense mutation was identified in 16%, 68%, and 81% of severe, moderate, or mild HA, respectively. They included 105 missense mutations (48%), 41 small deletions (19%), 25 splice site mutations (12%), 24 nonsense mutations (11%), 18 insertions (8%), three large deletions (1%), and one deletion plus insertion. Unreported mutations were distributed throughout the F8 gene, as they affected all F8 exons but exon 20. We report a wide spectrum of mutations collected in a large National database. The type of mutation was a strong predictor of the clinical phenotype. This database is expected to considerably improve the genetic counseling and medical care of HA families in Italy.

[Genetic anomalies of pancreatic carcinoma and clinical applications]. / Le anomalie genetiche del carcinoma pancreatico e le applicazioni cliniche.

Pancreatic cancer is a dismal disease. The 5-years overall survival ranges from 1% to 5%. Surgery is the only curative treatment available. Survival of selected patients with small lesion (< 2 cm) confined to the pancreas is improved to 19-41%. Presently the major effort is on studies of the cancer development phenomena to improve detection of patients with early lesions. The analysis of oncogene and tumor-suppressor gene activation may enable us to better define and cure this disease. Molecular genetic new tecnquiques performed on pancreatic juice, duodenal juice and stool, probably are the most promising new approach for early diagnosis of pancreatic cancer. This could be the right path to diagnose pancreatic malignant lesions at a curable stage, and to discriminate patients with a more favourable prognosis candidates to be submitted to adjuvant therapy with a curative intent, and also to discriminate real pancreatic cancer from patients with chronic pancreatitis.