Functional and structural analysis of four novel mutations of CYP21A2 gene in Italian patients with 21-hydroxylase deficiency.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by defects in the 21-hydroxylase gene (CYP21A2), coding for the enzyme 21-hydroxylase (21-OH). About 95% of the mutations arise from gene conversion between CYP21A2 and the inactive pseudogene CYP21A1P: only 5% are novel CYP21A2 mutations, in which functional analysis of mutant enzymes has been helpful to correlate genotype-phenotype. In the present study, we describe 3 novel point mutations (p.L122P, p.Q481X, and p.E161X) in 3 Italian patients with CAH: the fourth mutation (p.M150R) was found in the carrier state. Molecular modeling suggests a major impact on 21-hydroxylase activity, and functional analysis after expression in COS-7 cells confirms reduced enzymatic activity of the mutant enzymes. Only the p.M150R mutation affected the activity to a minor extent, associated with NC CAH. CYP21A2 genotyping and functional characterization of each disease-causing mutation has relevance both for treatment and genetic counseling to the patients.

Effectiveness of regional anaesthesia for treatment of facial and hand wounds by emergency physicians: A 9-month prospective study.

OBJECTIVE: We compared the effectiveness of nerve blocks (regional anaesthesia, [RA]) versus local anaesthesia (LA) to treat face and hand wounds. Emergency physicians who had not previously used nerve blocks administered the anaesthesia based on anatomic landmarks. METHODS: This prospective observational open study was conducted at a military teaching hospital emergency department (ED) between May 1, 2013 and January 31, 2014. All patients requiring treatment of facial or hand wounds were included. The primary outcome was anaesthesia effectiveness 15minutes post-administration. We also recorded the number of injections sites, injected volume, pain of administration, operator comfort, and complications. Lidocaine anaesthesia without epinephrine was used. RESULTS: Of the 1090 treated patients, 617 patients were included in the analysis: 316 with hand wounds and 301 with facial wounds. Overall, 130 wrist blocks and 63 facial blocks were performed. RA effectiveness was comparable to that of LA: for facial wounds, RA=88.9% versus LA=89% (P=0.86); for hand wounds, RA=82.2% versus LA=90.1% (P=0.15). RA groups had significantly fewer injections than the LA groups, and less anesthetic was injected in the facial RA group. The pain of anaesthesia administration and operator comfort was similar. There was no complication during the 9-month data collection period. CONCLUSION: Facial and wrist nerve blocks are easy to administer and as efficient as local infiltrations, plus they require fewer injection sites, and, for facial RA, less anesthetic. Their teaching and use should be more widespread in EDs.