Mutational, Functional, and Expression Studies of the TCF4 Gene in Pitt-Hopkins Syndrome

被引：123

作者：

de Pontual, Loic ^{[2
]}

Mathieu, Yves ^{[2
]}

Golzio, Christelle ^{[2
]}

Rio, Marlene ^{[1
]}

Malan, Valerie ^{[2
]}

Boddaert, Nathalie ^{[3
]}

Soufflet, Christine ^{[4
]}

Picard, Capucine ^{[5
,6
]}

Durandy, Anne ^{[5
]}

Dobbie, Angus ^{[7
]}

Heron, Delphine ^{[8
]}

Isidor, Bertrand ^{[9
]}

Motte, Jacques ^{[10
]}

Newburry-Ecob, Ruth ^{[11
]}

Pasquier, Laurent ^{[12
]}

Tardieu, Marc ^{[13
]}

Viot, Geraldine ^{[14
]}

Jaubert, Francis ^{[15
]}

Munnich, Arnold ^{[1
,2
]}

Colleaux, Laurence ^{[2
]}

Vekemans, Michel ^{[1
,2
]}

Etchevers, Heather ^{[2
]}

Lyonnet, Stanislas ^{[1
,2
]}

Amiel, Jeanne ^{[1
,2
]}

机构：

[1] Hop Necker Enfants Malad, Dept Genet, AP HP, Serv Genet & Cytogenet, F-75743 Paris 15, France

[2] Univ Paris 05, INSERM, Fac Med, U781, Paris, France

[3] Hop Necker Enfants Malad, INSERM, U797, F-75743 Paris 15, France

[4] Hop Necker Enfants Malad, INSERM, Serv Neurophysiol, U663, F-75743 Paris 15, France

[5] Hop Necker Enfants Malad, INSERM, U768, F-75743 Paris 15, France

[6] Univ Paris 05, Study Ctr Immunodeficiencies, Paris, France

[7] St James Univ Hosp, Genet Serv, Leeds, W Yorkshire, England

[8] Hop La Pitie Salpetriere, Dept Genet, Paris, France

[9] Hop Hotel Dieu, Serv Genet, Nantes, France

[10] CHU Reims, Amer Mem Hosp, Serv Neurol Pediat, Reims, France

[11] Dept Clin Genet, Bristol BS2 8EG, Avon, England

[12] Hop Sud, Serv Genet Clin, Rennes, France

[13] Hop Bicetre, Serv Neurol Pediat, Le Kremlin Bicetre, France

[14] Hop Cochin, Serv Genet, F-75674 Paris, France

[15] Hop Necker Enfants Malad, Serv Anat Pathol, F-75743 Paris 15, France

来源：

HUMAN MUTATION | 2009年 / 30卷 / 04期

关键词：

Pitt-Hopkins; TCF4; bHLH; E-protein; mental retardation; MENTAL-RETARDATION; TRANSCRIPTION FACTOR; E2-2; HAPLOINSUFFICIENCY; DIFFERENTIATION; PROTEINS; REVEALS; BINDING; DOSAGE; HASH-1;

D O I：

10.1002/humu.20935

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Pitt-Hopkins syndrome is a severe congenital encephalopathy recently ascribed to de novo heterozygous TCF4 gene mutations. we report a series of 13 novel PHS cases with a TCF4 mutation and show that EEG, brain magnetic resonance imagain (MRI), and immunological investigations provide valuable additional clues to the diagnosis. We confirm a mutational hot spot in the basic domain of the E-protein. Functional studies illustrate that heterodimerisation of mutant TCF4 proteins with a tissue-specific transcription factor is less effective than that homodimerisation in a luciferase reporter assay. We also show that the TCF4 expression pattern in human embryonic development is widespread but not ubiquitous. In summary, we further delineate an underdiagnosed mental retardation syndrome, highlighting TCF4 function during development and facilitating diagnosis within the first year of life. Hum Mutat 30, 669-676, 2009. (C) 2009 Wiley Liss, Inc.

引用

页码：669 / 676

页数：8

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