Auteurs
Zanella S - Tauber M - Muscatelli F
Journal
Respiratory physiology & neurobiology
Abstract
Prader-Willi syndrome (PWS) is a multigenic disorder caused by the loss of paternal expression of genes in the 15q11-q13 region. It is a complex and progressive disease. From birth, patients present breathing disorders (apnea, rhythm instability, hypoventilation and blunted response to changes in CO(2) or O(2)). Recent advances allowing early diagnosis permitted to prevent obesity of PWS patients and to alleviate some symptoms mainly by growth hormone therapy but there is no therapy to alleviate all symptoms and respiratory distress in particular. To further understand PWS several mutant mice, in which each candidate gene has been separately inactivated, have been developed and shown variable symptoms depending on the genes inactivated. Among them the Necdin deficiency appears to be responsible for breathing disorders. In Necdin deficient mice, respiratory defects resembling PWS have been shown in vivo and in vitro. These defects are central from origin and are correlated with biochemical and anatomical anomalies of the respiratory regulatory systems including serotonergic alterations.