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; Marie Luise Bisgaard

doi:10.1159/000328404

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, Marie Luise Bisgaard

14 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Subject Guide to Books in Print
Vol/bind	222
Udgave nummer	4
Sider (fra-til)	292-6
Antal sider	5
ISSN	0000-0159
DOI	https://doi.org/10.1159/000328404
Status	Udgivet - sep. 2011

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10.1159/000328404

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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 {M{\o}lgaard Poulsen}, {Marie Louise} and S{\o}rensen, {Flemming Brandt} and Bisgaard, {Marie Luise}",

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year = "2011",

month = sep,

doi = "10.1159/000328404",

language = "English",

volume = "222",

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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 - Mølgaard Poulsen, Marie Louise

AU - Sørensen, Flemming Brandt

AU - Bisgaard, Marie Luise

PY - 2011/9

Y1 - 2011/9

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

C2 - 21720150

SN - 0000-0159

VL - 222

SP - 292

EP - 296

JO - Subject Guide to Books in Print

JF - Subject Guide to Books in Print

IS - 4

ER -

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

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