Lack of mutation-histopathology correlation in a patient with Proteus syndrome.
Lack of mutation-histopathology correlation in a patient with Proteus syndrome.
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DOI：
10.1002/ajmg.a.37612
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发表时间：
2016-06
影响因子：
2
通讯作者：
Biesecker, Leslie G.
中科院分区：
文献类型：
--
作者：
Doucet, Meggie E.;Bloomhardt, Hadley M.;Moroz, Krzysztof;Lindhurst, Marjorie J.;Biesecker, Leslie G.
Proteus syndrome (PS) is characterized by progressive, disproportionate, segmental overgrowth and tumor susceptibility caused by a somatic mosaic AKT1 activating mutation. Each individual has unique manifestations making this disorder extremely heterogeneous. We correlated three variables in 38 tissue samples from a patient who died with PS: the gross affection status, the microscopic affection status, and the mutation level. The AKT1 mutation was measured using a PCR-based RFLP assay. Thirteen samples were grossly normal; six had detectable mutation (2-29%) although four of these six were histopathologically normal. Of the seven grossly normal samples that had no mutation, only four were histologically normal. The mutation level in the grossly abnormal samples was 3-35% and all but the right and left kidneys, skull, and left knee bone, with mutation levels of 19%, 15%, 26%, and 17% respectively, had abnormal histopathology. The highest mutation level was in a toe bone sample while the lowest levels were in the soft tissue surrounding that toe, and an omental fat nodule. We also show here that PS overgrowth can be caused by cellular proliferation or by extracellular matrix expansion. Additionally, papillary thyroid carcinoma was identified, a tumor not previously associated with PS. We conclude that gross pathology and histopathology correlate poorly with mutation levels in PS, that overgrowth can be mediated by cellular proliferation or extracellular matrix expansion, and that papillary thyroid carcinoma is part of the tumor susceptibility of PS. New methods need to be developed to facilitate genotype-phenotype correlation in mosaic disorders.
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DOI：
10.1056/nejmoa1104017
发表时间：
2011-08-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Lindhurst MJ;Sapp JC;Teer JK;Johnston JJ;Finn EM;Peters K;Turner J;Cannons JL;Bick D;Blakemore L;Blumhorst C;Brockmann K;Calder P;Cherman N;Deardorff MA;Everman DB;Golas G;Greenstein RM;Kato BM;Keppler-Noreuil KM;Kuznetsov SA;Miyamoto RT;Newman K;Ng D;O'Brien K;Rothenberg S;Schwartzentruber DJ;Singhal V;Tirabosco R;Upton J;Wientroub S;Zackai EH;Hoag K;Whitewood-Neal T;Robey PG;Schwartzberg PL;Darling TN;Tosi LL;Mullikin JC;Biesecker LG
通讯作者：
Biesecker LG
影响因子：
5.2
作者：
Biesecker, Leslie
通讯作者：
Biesecker, Leslie
DOI：
10.1002/ajmg.1320570117
发表时间：
1995-05-22
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
GORDON, PL;WILROY, RS;COHEN, MM
通讯作者：
COHEN, MM
影响因子：
13.8
作者：
Twede, JV;Turner, JT;Darling, TN
通讯作者：
Darling, TN
影响因子：
120.7
作者：
Biesecker, LG
通讯作者：
Biesecker, LG