These two authors contributed equally to this work.
CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin
Article first published online: 27 MAY 2011
© 2011 John Wiley & Sons A/S
Volume 81, Issue 3, pages 234–239, March 2012
How to Cite
Pauli, S., von Velsen, N., Burfeind, P., Steckel, M., Mänz, J., Buchholz, A., Borozdin, W. and Kohlhase, J. (2012), CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin. Clinical Genetics, 81: 234–239. doi: 10.1111/j.1399-0004.2011.01701.x
- Issue published online: 31 JAN 2012
- Article first published online: 27 MAY 2011
- Accepted manuscript online: 7 MAY 2011 03:58AM EST
- Received 15 March 2011, revised and accepted for publication 2 May 2011
- CHARGE syndrome;
- parental origin;
- paternal age
Pauli S, von Velsen N, Burfeind P, Steckel M, Mänz J, Buchholz A, Borozdin W, Kohlhase J. CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin.
CHARGE (coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies and deafness) syndrome is a congenital malformation syndrome caused by mutations in the CHD7 gene in approximately 2/3 of cases. In the vast majority of cases, CHARGE syndrome is sporadic. There are only a few reports of parent-to-child transmission and somatic or gonadal mosaicism. To determine the parental origin of CHD7 mutations in sporadic CHARGE syndrome, we screened 30 families for informative exonic or intronic polymorphisms located near the detected CHD7 mutation. An informative polymorphism could be identified in 13 out of 30 families. Linkage analysis was performed between the CHD7 mutation and the polymorphism in the child. In 12 out of 13 families, the mutation affected the paternal allele (92.3%). In our cohort, the mean paternal age at birth was 32.92 years. Comparing the age of fathers of an affected CHARGE patient with the paternal age of the German population in general, we could not observe any paternal age effect. Taken together, we show in this study that de novo CHD7 mutations occur predominantly in the male germ line.