Molecular characterization of Spanish patients with MECP2 duplication syndrome

被引：20

作者：

Pascual-Alonso, Ainhoa ^{[1
]}

Blasco, Laura ^{[1
]}

Vidal, Silvia ^{[1
]}

Gean, Esther ^{[2
]}

Rubio, Patricia ^{[2
]}

O'Callaghan, Mar ^{[3
]}

Martinez-Monseny, Antonio F. ^{[2
]}

Castells, Alba Aina ^{[1
,4
]}

Xiol, Clara ^{[1
]}

Catala, Vicenc ^{[5
]}

Brandi, Nuria ^{[6
]}

Pacheco, Paola ^{[6
]}

Ros, Carlota ^{[6
]}

del Campo, Miguel ^{[7
]}

Guillen, Encarna ^{[8
]}

Ibanez, Salva ^{[8
]}

Sanchez, Maria J. ^{[8
]}

Lapunzina, Pablo ^{[9
,10
]}

Nevado, Julian ^{[9
,10
]}

Santos, Fernando ^{[9
]}

Lloveras, Elisabet ^{[11
]}

Ortigoza-Escobar, Juan D. ^{[3
]}

Tejada, Maria, I ^{[10
,12
]}

Maortua, Hiart ^{[10
,12
]}

Martinez, Francisco ^{[13
]}

Orellana, Carmen ^{[13
]}

Rosello, Monica ^{[13
]}

Mesas, Maria A. ^{[14
]}

Obon, Maria ^{[15
]}

Plaja, Alberto ^{[16
]}

Fernandez-Ramos, Joaquin A. ^{[17
]}

Tizzano, Eduardo ^{[18
]}

Marin, Rosario ^{[19
]}

Pena-Segura, Jose L. ^{[20
]}

Alcantara, Soledad ^{[4
]}

Armstrong, Judith ^{[6
,10
,21
]}

机构：

[1] Fdn San Juan de Dios, Serv Med Genet & Mol, Barcelona, Spain

[2] Hosp Univ San Juan de Dios, Dept Med Genet & Mol, Barcelona, Spain

[3] Hosp Univ San Juan de Dios, Dept Neurol Pediat, Barcelona, Spain

[4] Univ Barcelona, Inst Neurociencies, Dept Patol & Terapeut Expt, Neural Dev Lab,IDIBELL, Barcelona, Spain

[5] Univ Autonoma Barcelona, Dept BCFyI, Unidad Biol Celular & Genet Med, Barcelona, Spain

[6] Hosp Univ San Juan de Dios, Serv Med Genet & Mol, Barcelona, Spain

[7] Hosp Valle De Hebron, Genet Epidemiol, Pediat, Barcelona, Spain

[8] Hosp Virgen Arrixaca, Unidad Genet, Murcia, Spain

[9] Hosp Univ La Paz, Inst Genet Med & Mol, Madrid, Spain

[10] Inst Salud Carlos III, CIBERER Biomed Network Res Ctr Rare Dis, Madrid, Spain

[11] LABCO Iberia, Dept Genet, Barcelona, Spain

[12] Hosp Univ Cruces, Inst Invest Sanitaria Biocruces, Serv Genet, Lab Genet Mol, Baracaldo, Spain

[13] Hosp Univ & Politecn La Fe, Unidad Genet, Valencia, Spain

[14] Hosp Xanit, Gastroenterol, Malaga, Spain

[15] Lab ICS, Area Genet Clin & Consell Genet, Girona, Spain

[16] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Inst Recerca VHIR, Barcelona, Spain

[17] Hosp Univ Reina Sofia, Unidad Neuropediat, Cordoba, Spain

[18] Hosp Univ Vall dHebron, Area Genet Clin & Mol, Barcelona, Spain

[19] Hosp Univ Puerta del Mar, Unidad Genet, Cadiz, Spain

[20] Hosp Univ Miguel Servet, Unidad Neuropediat, Zaragoza, Spain

[21] Hosp St Joan de Deu, Inst Recerca Pediat, Barcelona, Spain

来源：

CLINICAL GENETICS | 2020年 / 97卷 / 04期

关键词：

genotype-phenotype correlation; hypotonia; intellectual disability; IRAK1; MECP2; duplication; Methyl-CpG-binding protein 2 (MECP2); recurrent infections; Xq28-duplication; SEVERE MENTAL-RETARDATION; RETT-SYNDROME; INCLUDING MECP2; PHENOTYPE; GENE; FEMALES; RESCUE; GIRL;

D O I：

10.1111/cge.13718

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder characterized by a severe to profound intellectual disability, early onset hypotonia and diverse psycho-motor and behavioural features. To date, fewer than 200 cases have been published. We report the clinical and molecular characterization of a Spanish MDS cohort that included 19 boys and 2 girls. Clinical suspicions were confirmed by array comparative genomic hybridization and multiplex ligation-dependent probe amplification (MLPA). Using, a custom in-house MLPA assay, we performed a thorough study of the minimal duplicated region, from which we concluded a complete duplication of both MECP2 and IRAK1 was necessary for a correct MDS diagnosis, as patients with partial MECP2 duplications lacked some typical clinical traits present in other MDS patients. In addition, the duplication location may be related to phenotypic severity. This observation may provide a new approach for genotype-phenotype correlations, and thus more personalized genetic counselling.

引用

页码：610 / 620

页数：11

共 31 条

[1] ALLEN RC, 1992, AM J HUM GENET, V51, P1229
[2] Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome
Bauer, Michael
Koelsch, Uwe
Krueger, Renate
Unterwalder, Nadine
Hameister, Karin
Kaiser, Fabian Marc
Vignoli, Aglaia
Rossi, Rainer
Pilar Botella, Maria
Budisteanu, Magdalena
Rosello, Monica
Orellana, Carmen
Isabel Tejada, Maria
Papuc, Sorina Mihaela
Patat, Oliver
Julia, Sophie
Touraine, Renaud
Gomes, Thusari
Wenner, Kirsten
Xu, Xiu
Afenjar, Alexandra
Toutain, Annick
Philip, Nicole
Jezela-Stanek, Aleksandra
Gortner, Ludwig
Martinez, Francisco
Echenne, Bernard
Wahn, Volker
Meisel, Christian
Wieczorek, Dagmar
El-Chehadeh, Salima
Van Esch, Hilde
von Bernuth, Horst
[J]. JOURNAL OF CLINICAL IMMUNOLOGY, 2015, 35 (02) : 168 - 181
[3] Xq28 duplications including MECP2 in five females: Expanding the phenotype to severe mental retardation
Bijlsma, E. K.
Collins, A.
Papa, F. T.
Tejada, M. I.
Wheeler, P.
Peeters, E. A. J.
Gijsbers, A. C. J.
de Kamp, J. M. van
Kriek, M.
Losekoot, M.
Broekma, A. J.
Crolla, J. A.
Pollazzon, M.
Mucciolo, M.
Katzaki, E.
Disciglio, V.
Ferreri, M. I.
Marozza, A.
Mencarelli, M. A.
Castagnini, C.
Dosa, L.
Ariani, F.
Mari, F.
Canitano, R.
Hayek, G.
Botella, M. P.
Gener, B.
Minguez, M.
Renieri, A.
Ruivenkamp, C. A. L.
[J]. EUROPEAN JOURNAL OF MEDICAL GENETICS, 2012, 55 (6-7) : 404 - 413
[4] The revision of the Declaration of Helsinki: past, present and future
Carlson, RV
Boyd, KM
Webb, DJ
[J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2004, 57 (06) : 695 - 713
[5] Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance
Clayton-Smith, Jill
Walters, Sarah
Hobson, Emma
Burkitt-Wright, Emma
Smith, Rupert
Toutain, Annick
Amiel, Jeanne
Lyonnet, Stanislas
Mansour, Sahar
Fitzpatrick, David
Ciccone, Roberto
Ricca, Ivana
Zuffardi, Orsetta
Donnai, Dian
[J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2009, 17 (04) : 434 - 443
[6] Buccal swab as a reliable predictor for X inactivation ratio in inaccessible tissues
de Hoon, Bas
Monkhorst, Kim
Riegman, Peter
Laven, Joop S. E.
Gribnau, Joost
[J]. JOURNAL OF MEDICAL GENETICS, 2015, 52 (11) : 784 - 790
[7] Rett syndrome - biological pathways leading from MECP2 to disorder phenotypes
Ehrhart, Friederike
Coort, Susan L. M.
Cirillo, Elisa
Smeets, Eric
Evelo, Chris T.
Curfs, Leopold M. G.
[J]. ORPHANET JOURNAL OF RARE DISEASES, 2016, 11
[8] Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?
El Chehadeh, S.
Touraine, R.
Prieur, F.
Reardon, W.
Bienvenu, T.
Chantot-Bastaraud, S.
Doco-Fenzy, M.
Landais, E.
Philippe, C.
Marle, N.
Callier, P.
Mosca-Boidron, A. -L.
Mugneret, F.
Le Meur, N.
Goldenberg, A.
Guerrot, A. -M.
Chambon, P.
Satre, V.
Coutton, C.
Jouk, P. -S.
Devillard, F.
Dieterich, K.
Afenjar, A.
Burglen, L.
Moutard, M. -L.
Addor, M. -C.
Lebon, S.
Martinet, D.
Alessandri, J. -L.
Doray, B.
Miguet, M.
Devys, D.
Saugier-Veber, P.
Drunat, S.
Aral, B.
Kremer, V.
Rondeau, S.
Tabet, A. -C.
Thevenon, J.
Thauvin-Robinet, C.
Perreton, N.
Des Portes, V.
Faivre, L.
[J]. CLINICAL GENETICS, 2017, 91 (04) : 576 - 588
[9] MeCP2 as an Activator of Gene Expression
Horvath, Patricia M.
Monteggia, Lisa M.
[J]. TRENDS IN NEUROSCIENCES, 2018, 41 (02) : 72 - 74
[10] Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice
Kishi, Noriyuki
MacDonald, Jessica L.
Ye, Julia
Molyneaux, Bradley J.
Azim, Eiman
Macklis, Jeffrey D.
[J]. NATURE COMMUNICATIONS, 2016, 7

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