Monozygotic twins discordant for neurofibromatosis type 1 due to a postzygotic NF1 gene mutation

Vogt, Julia, Kohlhase, Jürgen, Morlot, Susanne, Kluwe, Lan, Mautner, Victor-Felix, Cooper, David Neil ORCID: https://orcid.org/0000-0002-8943-8484 and Kehrer-Sawatzki, Hildegard 2011. Monozygotic twins discordant for neurofibromatosis type 1 due to a postzygotic NF1 gene mutation. Human Mutation 32 (6) , E2134-E2147. 10.1002/humu.21476

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Abstract

The analysis of monozygotic twins (MZ) concordant for neurofibromatosis type 1 (NF1) has indicated that genetic factors exert a major influence on the clinical variability (e.g. the number of café-au-lait spots and/or neurofibromas) evident in this disease. Here, we report on a pair of monozygotic, dichorionic twins who are phenotypically discordant with respect to NF1. Whereas DNA sequence analysis indicated somatic mosaicism for the NF1 nonsense mutation, c.4108C>T (p.Q1370X), in the affected twin II/1, this lesion was apparently absent in his unaffected brother. The observation of heterozygosity for flanking SNP and microsatellite markers rendered it most unlikely that the observed mosaicism with normal cells was due to mutation reversion brought about either by gene conversion or mitotic recombination. Instead, we conclude that the twinning event, which would have taken place within three days post-fertilization, must have preceded the c.4108C>T mutation which is therefore predicted to have occurred during the blastocyst stage, leading to somatic mosaicism with normal cells lacking the mutation. This is the first reported case of monozygotic twins discordant for NF1 in whom mosaicism for a postzygotic NF1 gene mutation has been observed in the affected but not the unaffected twin.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords:	Neurofibromatosis type 1 ; Monozygotic twins ; Phenotype discordance ; Mosaicism ; Postzygotic mutation
Additional Information:	Mutation in Brief
Publisher:	John Wiley & Sons
ISSN:	1059-7794
Last Modified:	19 Oct 2022 09:59
URI:	https://orca.cardiff.ac.uk/id/eprint/22841

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