Premium
Monozygotic twins discordant for neurofibromatosis type 1 due to a postzygotic NF1 gene mutation
Author(s) -
Vogt Julia,
Kohlhase Jürgen,
Morlot Susanne,
Kluwe Lan,
Mautner VictorFelix,
Cooper David N.,
KehrerSawatzki Hildegard
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21476
Subject(s) - germline mosaicism , biology , genetics , monozygotic twin , loss of heterozygosity , mutation , nonsense mutation , neurofibromatosis , germline mutation , allele , gene , missense mutation
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. © 2011 Wiley‐Liss, Inc.