Clin Genet. 2011 May 7. doi: 10.1111/j.1399-0004.2011.01701.x. [Epub ahead of print]

Clin Genet. 2011 May 7. doi: 10.1111/j.1399-0004.2011.01701.x. [Epub ahead of print]


CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin.

Pauli S, von Velsen N, Burfeind P, Steckel M, Mänz J, Buchholz A, Borozdin W, Kohlhase J.

SourceInstitute of Human Genetics, University of Göttingen, Germany Center for Human Genetics, Freiburg, Germany.



Abstract

CHARGE syndrome is a congenital malformation syndrome caused in approximately 2/3 of cases by mutations in the CHD7 gene. 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 demonstrate in the present study that de novo CHD7 mutations occur predominantly in the male germ line.



© 2011 John Wiley & Sons A/S.