Screening of mutations in genes that predispose to hereditary paragangliomas and pheochromocytomas.

Thirty per cent of the paragangliomas and pheochromocytomas reported are hereditary. Mutations in SDHB, SDHC, SDHD, and more recently SDHAF2 and TMEM127 genes have been described in these hereditary tumors. We looked for mutations in these 5 genes in a series of 269 patients with paragangliomas and/or pheochromocytomas. The SDHB, SDHC, and SDHD genes were analyzed in a series of 269 unrelated index patients with paragangliomas and/or pheochromocytomas using dHPLC screening of point mutations followed by direct sequencing and Multiplex PCR Liquid Chromatography to detect large rearrangements confirmed by quantitative PCR. In a second phase, we adapted Multiplex PCR Liquid Chromatography to the SDHAF2 and TMEM127 genes. This method and direct sequencing were applied to 230 patients without the SDHB, C, D mutations. Of the 269 patients, 44 carried a mutation (16.3%). Thirty-seven different mutations were identified: 18 in SDHB (including 2 large deletions), 8 in SDHD, 6 in SDHC, 5 in TMEM127, and no mutations in SDHAF2. Thirteen mutations have not been published so far. An exhaustive study of the different genes is needed to make possible a familial genetic diagnosis in paraganglioma and pheochromocytoma hereditary syndromes. Although mutations in SDHC and TMEM127 are less frequent than mutations in SDHB and SDHD, they also have less evident clinical feature indicators. Analyzing SDHAF2 must be restricted to familial extra-adrenal paragangliomas. Multiplex PCR Liquid Chromatography is a sensitive, fast, and inexpensive method for screening large rearrangements, which are infrequent in these syndromes.

[Screening and management of glucose metabolism disorders in cystic fibrosis patients. Practices survey in 4 French reference centers]. / Dépistage et prise en charge des troubles du métabolisme glucidique chez les patients atteints de mucoviscidose. Etude de pratiques au sein du réseau EMERA.

OBJECTIVE: Glucose metabolism disorders are a new point of interest in cystic fibrosis (CF) management. Cystic fibrosis-related diabetes mellitus (CFRD) increases alteration of pulmonary function as well as patients' morbidity and mortality. In France, CF patients are exclusively followed up in reference centers. We conducted a practices survey on screening and diagnosis of glucose metabolism disorders at 4 French CF centers. The objective of this study was to assess adherence to practice guidelines developed in 2002 at these centers. METHODS: This study was conducted in 2 sessions: 60 medical records were randomly selected in 2005 and in 2007 for patients aged over 10 years followed up at 4 CF centers. A questionnaire survey was completed for each patient with questions on CFRD screening, diagnosis, monitoring and treatment. Our guidelines recommend random blood glucose (RBG) at each standard biological test, annual glycosylated haemoglobin and an oral glucose tolerance test (OGTT) at 10, 15 and 18 years of age, then every 2 or 3 years. RESULTS: An annual RBG was performed in 82% of patients in 2005 and 91.5% in 2007. HbA1c screening was performed annually for 77% of patients in the 1st session and for 90% of patients for the 2nd session (p<0.10). Adherence to OGTT guidelines was better for adults than children: 96% had an OGTT during the 3 years of the first session and 79% during the second session, while fewer than 50% of children had their OGTT at 15 and 18 years of age. Taking the OGTT at 10 years of age could not be assessed because no patients were 10 years old during the study period. Screening for neurological complications of CFRD was assessed in the majority of diabetic patients, while half or less than half had annual fundus oculi or microalbuminuria dosage. DISCUSSION: There was an improvement in screening for CFRD and glucose metabolism disorders between 2005 and 2007, even though practices could still be improved. This shows that clinical guidelines can be implemented and followed. However, screening and management criteria for glucose metabolism disorders must be consensus-based with higher evidence in order to limit the variability of practices and prevent CFRD-related complications.