Germline and somatic mosaicism for FGFR2 mutation in the mother of a child with Crouzon syndrome:

Am J Med Genet A. 2010 Jul 15. [Epub ahead of print]

Germline and somatic mosaicism for FGFR2 mutation in the mother of a child with Crouzon syndrome: Implications for genetic testing in "paternal age-effect" syndromes.
Goriely A, Lord H, Lim J, Johnson D, Lester T, Firth HV, Wilkie AO.

Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

Abstract
Crouzon syndrome is a dominantly inherited disorder characterized by craniosynostosis and facial dysostosis, caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene; it belongs to a class of disorders that mostly arise as de novo mutations and exhibit a near-exclusive paternal origin of mutation and elevated paternal age ("paternal age effect"). However, even if this is the major mode of origin of mutations in paternal age-effect disorders, germline mosaicism may also occur. Here we describe the first molecularly documented evidence of germline and somatic mosaicism for FGFR2 mutation, identified in the mother of a child with Crouzon syndrome caused by a heterozygous c.1007A>G (p.Asp336Gly) substitution. Levels of maternal somatic mosaicism for this mutation, estimated by pyrosequencing, ranged from 3.3% in hair roots to 14.1% in blood. Our observation underlines the importance of parental molecular testing for accurate genetic counseling of the risk of recurrence for Crouzon, and other paternal age-effect syndromes. (c) 2010 Wiley-Liss, Inc.

PMID: 20635358 [PubMed - as supplied by publisher]