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.
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 or...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1797067089945559040 |
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| author | Goriely, A Lord, H Lim, J Johnson, D Lester, T Firth, H Wilkie, A |
| author_facet | Goriely, A Lord, H Lim, J Johnson, D Lester, T Firth, H Wilkie, A |
| author_sort | Goriely, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:51:20Z |
| format | Journal article |
| id | oxford-uuid:4b5e1ac6-c6f8-4750-bf39-c04b2d6c6360 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:51:20Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:4b5e1ac6-c6f8-4750-bf39-c04b2d6c63602022-03-26T15:43:11ZGermline and somatic mosaicism for FGFR2 mutation in the mother of a child with Crouzon syndrome: Implications for genetic testing in "paternal age-effect" syndromes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4b5e1ac6-c6f8-4750-bf39-c04b2d6c6360EnglishSymplectic Elements at Oxford2010Goriely, ALord, HLim, JJohnson, DLester, TFirth, HWilkie, ACrouzon 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. |
| spellingShingle | Goriely, A Lord, H Lim, J Johnson, D Lester, T Firth, H Wilkie, A 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. |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
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