Germline and Somatic Mosaicism for FGFR2 Mutation in the Mother of a Child With Crouzon Syndrome: Implications for Genetic Testing in ‘‘Paternal Age-Effect’’ SyndromesAm J Med Genet Part A (2010)
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 thatmostly 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.
- craniosynostosis; paternal age-effect disorders; Crouzon syndrome; germline mosaicism; FGFR2
Publication DateSpring April 24, 2010
Citation Informationjasmine Lim. "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" Am J Med Genet Part A (2010)
Available at: http://works.bepress.com/jasmine-lim/5/