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.

American Journal of Medical Genetics. Part a
Anne GorielyA O Wilkie

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.

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Citations

Dec 8, 2010·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Federico Di RoccoDominique Renier
Jan 21, 2011·European Journal of Human Genetics : EJHG·David Johnson, Andrew O M Wilkie
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Feb 14, 2012·American Journal of Human Genetics·Anne Goriely, Andrew O M Wilkie
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Mar 28, 2013·American Journal of Medical Genetics. Part a·Sally JayAndrew O M Wilkie
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Oct 29, 2020·Obstetrical & Gynecological Survey·Tara Kaur BrahDavid E Abel

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Methods Mentioned

BETA
PCR
restriction digest

Software Mentioned

Pyroseq
GeneMapper

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