Mosaicism in segmental darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues

Theresa Larriba Harboe, Patrick Willems, Cathrine Jespersgaard, Marie Louise Mølgaard Poulsen, Flemming Brandt Sørensen, Søs Marie Luise Bisgaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Darier disease is an autosomal dominant genodermatosis caused by germline mutations in the ATP2A2 gene. Clinical expression is variable, including rare segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic counseling of segmental Darier patients is complex, as risk of transmitting a nonsegmental phenotype to offspring is of unknown magnitude. We present the first in-depth molecular analysis of a mosaic patient with segmental disease, quantifying proportions of mutated and normal alleles in various tissues. Pyrosequence analysis of DNA from semen, affected and normal skin, peripheral leukocytes and hair revealed an uneven distribution of the mutated allele, from 14% in semen to 37% in affected skin. We suggest a model for segmental manifestation expression where a threshold number of mutated cells is needed for manifestation development. We further recommend molecular analysis of the ATP2A2 gene in semen of male patients with segmental Darier disease to improve genetic counseling.
OriginalsprogEngelsk
TidsskriftDermatology
Vol/bind222
Udgave nummer4
Sider (fra-til)292-6
Antal sider5
ISSN1018-8665
DOI
StatusUdgivet - 2011

Fingeraftryk

Mosaicism
Alleles
Genetic Counseling
Semen
Darier Disease
Skin
Germ-Line Mutation
Hair
DNA
Segmental Darier Disease

Citer dette

Harboe, Theresa Larriba ; Willems, Patrick ; Jespersgaard, Cathrine ; Poulsen, Marie Louise Mølgaard ; Sørensen, Flemming Brandt ; Bisgaard, Søs Marie Luise. / Mosaicism in segmental darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues. I: Dermatology. 2011 ; Bind 222, Nr. 4. s. 292-6.
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title = "Mosaicism in segmental darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues",
abstract = "Darier disease is an autosomal dominant genodermatosis caused by germline mutations in the ATP2A2 gene. Clinical expression is variable, including rare segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic counseling of segmental Darier patients is complex, as risk of transmitting a nonsegmental phenotype to offspring is of unknown magnitude. We present the first in-depth molecular analysis of a mosaic patient with segmental disease, quantifying proportions of mutated and normal alleles in various tissues. Pyrosequence analysis of DNA from semen, affected and normal skin, peripheral leukocytes and hair revealed an uneven distribution of the mutated allele, from 14{\%} in semen to 37{\%} in affected skin. We suggest a model for segmental manifestation expression where a threshold number of mutated cells is needed for manifestation development. We further recommend molecular analysis of the ATP2A2 gene in semen of male patients with segmental Darier disease to improve genetic counseling.",
author = "Harboe, {Theresa Larriba} and Patrick Willems and Cathrine Jespersgaard and Poulsen, {Marie Louise M{\o}lgaard} and S{\o}rensen, {Flemming Brandt} and Bisgaard, {S{\o}s Marie Luise}",
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Mosaicism in segmental darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues. / Harboe, Theresa Larriba; Willems, Patrick; Jespersgaard, Cathrine; Poulsen, Marie Louise Mølgaard; Sørensen, Flemming Brandt; Bisgaard, Søs Marie Luise.

I: Dermatology, Bind 222, Nr. 4, 2011, s. 292-6.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Mosaicism in segmental darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues

AU - Harboe, Theresa Larriba

AU - Willems, Patrick

AU - Jespersgaard, Cathrine

AU - Poulsen, Marie Louise Mølgaard

AU - Sørensen, Flemming Brandt

AU - Bisgaard, Søs Marie Luise

N1 - Copyright © 2011 S. Karger AG, Basel.

PY - 2011

Y1 - 2011

N2 - Darier disease is an autosomal dominant genodermatosis caused by germline mutations in the ATP2A2 gene. Clinical expression is variable, including rare segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic counseling of segmental Darier patients is complex, as risk of transmitting a nonsegmental phenotype to offspring is of unknown magnitude. We present the first in-depth molecular analysis of a mosaic patient with segmental disease, quantifying proportions of mutated and normal alleles in various tissues. Pyrosequence analysis of DNA from semen, affected and normal skin, peripheral leukocytes and hair revealed an uneven distribution of the mutated allele, from 14% in semen to 37% in affected skin. We suggest a model for segmental manifestation expression where a threshold number of mutated cells is needed for manifestation development. We further recommend molecular analysis of the ATP2A2 gene in semen of male patients with segmental Darier disease to improve genetic counseling.

AB - Darier disease is an autosomal dominant genodermatosis caused by germline mutations in the ATP2A2 gene. Clinical expression is variable, including rare segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic counseling of segmental Darier patients is complex, as risk of transmitting a nonsegmental phenotype to offspring is of unknown magnitude. We present the first in-depth molecular analysis of a mosaic patient with segmental disease, quantifying proportions of mutated and normal alleles in various tissues. Pyrosequence analysis of DNA from semen, affected and normal skin, peripheral leukocytes and hair revealed an uneven distribution of the mutated allele, from 14% in semen to 37% in affected skin. We suggest a model for segmental manifestation expression where a threshold number of mutated cells is needed for manifestation development. We further recommend molecular analysis of the ATP2A2 gene in semen of male patients with segmental Darier disease to improve genetic counseling.

U2 - 10.1159/000328404

DO - 10.1159/000328404

M3 - Journal article

VL - 222

SP - 292

EP - 296

JO - Dermatology

JF - Dermatology

SN - 1018-8665

IS - 4

ER -