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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.

Original publication

DOI

10.1002/ajmg.a.33513

Type

Journal article

Journal

Am J Med Genet A

Publication Date

08/2010

Volume

152A

Pages

2067 - 2073

Keywords

Adult, Child, Craniofacial Dysostosis, Craniosynostoses, DNA, Female, Genetic Testing, Germ-Line Mutation, Humans, Male, Mosaicism, Mothers, Paternal Age, Pedigree, Polymerase Chain Reaction, Receptor, Fibroblast Growth Factor, Type 2, Syndrome