Monozygotic twins discordant for neurofibromatosis type 1 due to a postzygotic NF1 gene mutation.
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Monozygotic twins discordant for neurofibromatosis type 1 due to a postzygotic NF1 gene mutation. / Vogt, Julia; Kohlhase, Jürgen; Morlot, Susanne; Kluwe, Lan; Mautner, Viktor Felix; Cooper, David N; Kehrer-Sawatzki, Hildegard.
In: HUM MUTAT, Vol. 32, No. 6, 6, 2011, p. 2134-2147.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Monozygotic twins discordant for neurofibromatosis type 1 due to a postzygotic NF1 gene mutation.
AU - Vogt, Julia
AU - Kohlhase, Jürgen
AU - Morlot, Susanne
AU - Kluwe, Lan
AU - Mautner, Viktor Felix
AU - Cooper, David N
AU - Kehrer-Sawatzki, Hildegard
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Humans
KW - Male
KW - Child, Preschool
KW - Mutation
KW - Phenotype
KW - Pedigree
KW - Polymorphism, Single Nucleotide
KW - Sequence Analysis, DNA
KW - Heterozygote
KW - Neurofibromin 1/genetics
KW - Mosaicism
KW - Neurofibromatosis 1/genetics
KW - Cafe-au-Lait Spots/genetics
KW - Twins, Monozygotic/genetics
KW - Zygote
KW - Humans
KW - Male
KW - Child, Preschool
KW - Mutation
KW - Phenotype
KW - Pedigree
KW - Polymorphism, Single Nucleotide
KW - Sequence Analysis, DNA
KW - Heterozygote
KW - Neurofibromin 1/genetics
KW - Mosaicism
KW - Neurofibromatosis 1/genetics
KW - Cafe-au-Lait Spots/genetics
KW - Twins, Monozygotic/genetics
KW - Zygote
M3 - SCORING: Journal article
VL - 32
SP - 2134
EP - 2147
JO - HUM MUTAT
JF - HUM MUTAT
SN - 1059-7794
IS - 6
M1 - 6
ER -