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Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: implications for genetic counseling in postzygotic mosaicism cases

Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: implications for genetic counseling in postzygotic mosaicism cases
Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: implications for genetic counseling in postzygotic mosaicism cases

We report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence-based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low-level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA. Mutation quantification was performed by deep next-generation sequencing (NGS) of DNA extracted from three somatic tissues (blood, fibroblasts, saliva) and a sperm sample. The mutation was detectable in all tissues tested, at levels ranging from 7% to 10% (mutation present in ∼20% of diploid somatic cells and 7% of haploid sperm), demonstrating the involvement of both somatic and gonadal lineages in this patient. This report illustrates the clinical utility of performing targeted NGS analysis on sperm from males with a mosaic condition in order to provide personalized transmission risk and offer evidence-based counseling on reproductive safety.

Journal Article
1059-7794
1360-1364
Bernkopf, Marie
8ed8582f-5c98-4e75-be1b-de5c0e14648b
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d
Koelling, Nils
7a663df3-0851-44f0-9c6d-8d81d9e4ab73
Morgan, Tim
06110bc7-5ac4-408f-a5bd-714515db58cd
Collins, Amanda L
3d548973-7ea9-4738-aafa-f9a2cc1b77c0
Fairhurst, Joanna
2812ed8e-8598-49bc-8919-52fecd2c0fef
Robertson, Stephen P
73dfe348-c5a6-4e7e-851e-55f3b27e4890
Douglas, Andrew G L
2c789ec4-a222-43bc-a040-522ca64fea42
Goriely, Anne
3062748d-d5fa-43ce-90df-7e3738e32d92
Bernkopf, Marie
8ed8582f-5c98-4e75-be1b-de5c0e14648b
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d
Koelling, Nils
7a663df3-0851-44f0-9c6d-8d81d9e4ab73
Morgan, Tim
06110bc7-5ac4-408f-a5bd-714515db58cd
Collins, Amanda L
3d548973-7ea9-4738-aafa-f9a2cc1b77c0
Fairhurst, Joanna
2812ed8e-8598-49bc-8919-52fecd2c0fef
Robertson, Stephen P
73dfe348-c5a6-4e7e-851e-55f3b27e4890
Douglas, Andrew G L
2c789ec4-a222-43bc-a040-522ca64fea42
Goriely, Anne
3062748d-d5fa-43ce-90df-7e3738e32d92

Bernkopf, Marie, Hunt, David, Koelling, Nils, Morgan, Tim, Collins, Amanda L, Fairhurst, Joanna, Robertson, Stephen P, Douglas, Andrew G L and Goriely, Anne (2017) Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: implications for genetic counseling in postzygotic mosaicism cases. Human Mutation, 38 (10), 1360-1364. (doi:10.1002/humu.23281).

Record type: Article

Abstract

We report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence-based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low-level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA. Mutation quantification was performed by deep next-generation sequencing (NGS) of DNA extracted from three somatic tissues (blood, fibroblasts, saliva) and a sperm sample. The mutation was detectable in all tissues tested, at levels ranging from 7% to 10% (mutation present in ∼20% of diploid somatic cells and 7% of haploid sperm), demonstrating the involvement of both somatic and gonadal lineages in this patient. This report illustrates the clinical utility of performing targeted NGS analysis on sperm from males with a mosaic condition in order to provide personalized transmission risk and offer evidence-based counseling on reproductive safety.

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Accepted/In Press date: 11 June 2017
e-pub ahead of print date: 21 June 2017
Published date: October 2017
Additional Information: © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.
Keywords: Journal Article

Identifiers

Local EPrints ID: 413676
URI: http://eprints.soton.ac.uk/id/eprint/413676
ISSN: 1059-7794
PURE UUID: 2bac1d51-375d-4e62-b960-d52d9415001f
ORCID for Andrew G L Douglas: ORCID iD orcid.org/0000-0001-5154-6714

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Date deposited: 31 Aug 2017 16:31
Last modified: 17 Dec 2019 01:41

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Contributors

Author: Marie Bernkopf
Author: David Hunt
Author: Nils Koelling
Author: Tim Morgan
Author: Amanda L Collins
Author: Joanna Fairhurst
Author: Stephen P Robertson
Author: Anne Goriely

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