Posch M.G.,Deutsches Herzzentrum Berlin |
Posch M.G.,Charité - Medical University of Berlin |
Waldmuller S.,Institute for Heart and Circulation Research |
Muller M.,Institute for Heart and Circulation Research |
And 13 more authors.
PLoS ONE | Year: 2011
Secundum-type atrial septal defects (ASDII) account for approximately 10% of all congenital heart defects (CHD) and are associated with a familial risk. Mutations in transcription factors represent a genetic source for ASDII. Yet, little is known about the role of mutations in sarcomeric genes in ASDII etiology. To assess the role of sarcomeric genes in patients with inherited ASDII, we analyzed 13 sarcomeric genes (MYH7, MYBPC3, TNNT2, TCAP, TNNI3, MYH6, TPM1, MYL2, CSRP3, ACTC1, MYL3, TNNC1, and TTN kinase region) in 31 patients with familial ASDII using array-based resequencing. Genotyping of family relatives and control subjects as well as structural and homology analyses were used to evaluate the pathogenic impact of novel non-synonymous gene variants. Three novel missense mutations were found in the MYH6 gene encoding alpha-myosin heavy chain (R17H, C539R, and K543R). These mutations co-segregated with CHD in the families and were absent in 370 control alleles. Interestingly, all three MYH6 mutations are located in a highly conserved region of the alpha-myosin motor domain, which is involved in myosin-actin interaction. In addition, the cardiomyopathy related MYH6-A1004S and the MYBPC3-A833T mutations were also found in one and two unrelated subjects with ASDII, respectively. No mutations were found in the 11 other sarcomeric genes analyzed. The study indicates that sarcomeric gene mutations may represent a so far underestimated genetic source for familial recurrence of ASDII. In particular, perturbations in the MYH6 head domain seem to play a major role in the genetic origin of familial ASDII. © 2011 Posch et al.
Trellu M.,Service de diabetologie pediatrique |
Lacombe S.,Institut Universitaire de France |
Morin D.,Service de diabetologie pediatrique |
Morin D.,Institute marin Saint Pierre |
And 2 more authors.
Archives de Pediatrie | Year: 2015
Since 1st January 2000, the PEDIAB-LR registry has listed new cases of diabetes in children under 16. years of age in the Languedoc-Roussillon region of France, in order to assess the incidence and epidemiological characteristics of children affected by diabetes. At the end of December 2010, 745 children had been registered. The characteristics of these children included an identical proportion of girls and boys, a mean age of 8. years at diagnosis, and a family history of type 1 diabetes in 8.4% of the cases. Inaugural ketoacidosis was observed in 69.5% of the patients and was severe in 23.7% of these cases. To replace intravenous insulin, a two-injection dosing regimen (in the morning and before dinner) was prescribed in 76.5% of cases, multi-injections of basal-bolus in 16%, and subcutaneous insulin infusion (insulin pump therapy) in 7.5% of cases. Between 2000 and 2010, there was no increase in overall incidence. It is noteworthy that age at diagnosis tended to decrease, but this was not statistically significant. In conclusion, the PEDIAB-LR registry is currently the only French registry on diabetes in children, analyzing many factors related to its incidence, such as age at diagnosis and the existence of ketoacidosis. © 2015 Elsevier Masson SAS.