A series of 38 novel germline and somatic mutations of NIPBL in Cornelia de Lange syndrome

被引：21

作者：

Nizon, M. ^{[1
]}

Henry, M. ^{[1
]}

Michot, C. ^{[1
]}

Baumann, C. ^{[2
]}

Bazin, A. ^{[3
]}

Bessieres, B. ^{[1
]}

Blesson, S. ^{[4
]}

Cordier-Alex, M. -P. ^{[5
]}

David, A. ^{[6
]}

Delahaye-Duriez, A. ^{[7
]}

Delezoide, A. -L. ^{[2
]}

Dieux-Coeslier, A. ^{[8
]}

Doco-Fenzy, M. ^{[9
]}

Faivre, L. ^{[10
]}

Goldenberg, A. ^{[11
]}

Layet, V. ^{[12
]}

Loget, P. ^{[13
]}

Marlin, S. ^{[1
]}

Martinovic, J. ^{[1
]}

Odent, S. ^{[14
]}

Pasquier, L. ^{[14
]}

Plessis, G. ^{[15
]}

Prieur, F. ^{[16
]}

Putoux, A. ^{[5
]}

Rio, M. ^{[1
]}

Testard, H. ^{[17
]}

Bonnefont, J. -P. ^{[1
]}

Cormier-Daire, V. ^{[1
]}

机构：

[1] Univ Paris 05, Inst IMAGINE, Dept Genet, Sorbonne Paris Cite,INSERM UMR1163,Hop Necker Enf, Paris, France

[2] CHU Robert Debre, Dept Genet, Paris, France

[3] CH Rene Dubos, Dept Genet, Pontoise, France

[4] CHRU Tours, Serv Genet, Hop Bretonneau, Tours, France

[5] Hosp Civils Lyon, Serv Genet Clin, Bron, France

[6] CHU Nantes, Gen Med Serv, F-44035 Nantes 01, France

[7] CHU Paris Seine St Denis, Serv Genet, Hop Jean Verdier, Bondy, France

[8] CHRU Lille, Serv Genet Clin, Hop Jeanne Flandre, F-59037 Lille, France

[9] CHU Reims, Serv Genet, Hop Maison Blanche, Reims, France

[10] CHU Dijon, Ctr Genet, Dijon, France

[11] CHU, Dept Genet, Rouen, France

[12] Hop Jacques Monod, Serv Genet Med, GH Havre, Le Havre, France

[13] Univ Rennes 1, Serv Anat & Cytol Pathol, Hop Pontchaillou, CHU, Rennes, France

[14] CHU Rennes, Serv Genet Clin, Hop Sud, Rennes, France

[15] CHU Clemenceau, Serv Genet Med, Caen, France

[16] CHU St Etienne, Serv Genet Clin, Hop Nord, St Priest En Jarez, France

[17] CHU Grenoble, Dept Pediat, F-38043 Grenoble, France

来源：

CLINICAL GENETICS | 2016年 / 89卷 / 05期

关键词：

buccal cells; Cornelia de Lange syndrome; NIPBL; somatic mosaicism; GENOTYPE-PHENOTYPE CORRELATION; GENETIC-HETEROGENEITY; NIPPED-B; MOSAICISM; INDIVIDUALS; HOMOLOG; PATIENT;

D O I：

10.1111/cge.12720

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to a heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: (i) intrauterine growth retardation and postnatal short stature, (ii) feeding difficulties and/or gastro-oesophageal reflux, (iii) microcephaly, (iv) intellectual disability, and (v) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and 3 in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for 20 cases which do not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counselling.

引用

页码：584 / 589

页数：6

共 18 条

[1] Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism [J].

Ansari, Morad ;

Poke, Gemma ;

Ferry, Quentin ;

Williamson, Kathleen ;

Aldridge, Roland ;

Meynert, Alison M. ;

Bengani, Hemant ;

Chan, Cheng Yee ;

Kayserili, Hulya ;

Avci, Sahin ;

Hennekam, Raoul C. M. ;

Lampe, Anne K. ;

Redeker, Egbert ;

Homfray, Tessa ;

Ross, Alison ;

Smeland, Marie Falkenberg ;

Mansour, Sahar ;

Parker, Michael J. ;

Cook, Jacqueline A. ;

Splitt, Miranda ;

Fisher, Richard B. ;

Fryer, Alan ;

Magee, Alex C. ;

Wilkie, Andrew ;

Barnicoat, Angela ;

Brady, Angela F. ;

Cooper, Nicola S. ;

Mercer, Catherine ;

Deshpande, Charu ;

Bennett, Christopher P. ;

Pilz, Daniela T. ;

Ruddy, Deborah ;

Cilliers, Deirdre ;

Johnson, Diana S. ;

Josifova, Dragana ;

Rosser, Elisabeth ;

Thompson, Elizabeth M. ;

Wakeling, Emma ;

Kinning, Esther ;

Stewart, Fiona ;

Flinter, Frances ;

Girisha, Katta M. ;

Cox, Helen ;

Firth, Helen V. ;

Kingston, Helen ;

Wee, Jamie S. ;

Hurst, Jane A. ;

Clayton-Smith, Jill ;

Tolmie, John ;

Vogt, Julie .

JOURNAL OF MEDICAL GENETICS, 2014, 51 (10) :659-668

[2] Somatic mosaicism in a Cornelia de Lange syndrome patient with NIPBL mutation identified by different next generation sequencing approaches [J].

Baquero-Montoya, C. ;

Gil-Rodriguez, M. C. ;

Braunholz, D. ;

Teresa-Rodrigo, M. E. ;

Obieglo, C. ;

Gener, B. ;

Schwarzmayr, T. ;

Strom, T. M. ;

Gomez-Puertas, P. ;

Puisac, B. ;

Gillessen-Kaesbach, G. ;

Musio, A. ;

Ramos, F. J. ;

Kaiser, F. J. ;

Pie, J. .

CLINICAL GENETICS, 2014, 86 (06) :595-597

[3] NIPBL mutations and genetic heterogeneity in Cornelia de Lange syndrome -: art. no. e128 [J].

Borck, G ;

Redon, R ;

Sanlaville, D ;

Rio, M ;

Prieur, M ;

Lyonnet, S ;

Vekemans, M ;

Carter, NP ;

Munnich, A ;

Colleaux, L ;

Cormier-Daire, V .

JOURNAL OF MEDICAL GENETICS, 2004, 41 (12) :e128

[4] Hidden Mutations in Cornelia de Lange Syndrome Limitations of Sanger Sequencing in Molecular Diagnostics [J].

Braunholz, Diana ;

Obieglo, Carolin ;

Parenti, Ilaria ;

Pozojevic, Jelena ;

Eckhold, Juliane ;

Reiz, Benedikt ;

Braenne, Ingrid ;

Wendt, Kerstin S. ;

Watrin, Erwan ;

Vodopiutz, Julia ;

Rieder, Harald ;

Gillessen-Kaesbach, Gabriele ;

Kaiser, Frank J. .

HUMAN MUTATION, 2015, 36 (01) :26-29

[5] Somatic mosaicism in Cornelia de Lange syndrome: a further contributor to the wide clinical expressivity? [J].

Castronovo, P. ;

Delahaye-Duriez, A. ;

Gervasini, C. ;

Azzollini, J. ;

Minier, F. ;

Russo, S. ;

Masciadri, M. ;

Selicorni, A. ;

Verloes, A. ;

Larizza, L. .

CLINICAL GENETICS, 2010, 78 (06) :560-564

[6] Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of Cornelia de Lange syndrome with predominant mental retardation [J].

Deardorff, Matthew A. ;

Kaur, Maninder ;

Yaeger, Dinah ;

Rampuria, Abhinav ;

Korolev, Sergey ;

Pie, Juan ;

Gil-Rodriguez, Concepcion ;

Arnedo, Maria ;

Loeys, Bart ;

Kline, Antonie D. ;

Wilson, Meredith ;

Lillquist, Kaj ;

Siu, Victoria ;

Ramos, Feliciano J. ;

Musio, Antonio ;

Jackson, Laird S. ;

Dorsett, Dale ;

Krantz, Ian D. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (03) :485-494

[7] HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle [J].

Deardorff, Matthew A. ;

Bando, Masashige ;

Nakato, Ryuichiro ;

Watrin, Erwan ;

Itoh, Takehiko ;

Minamino, Masashi ;

Saitoh, Katsuya ;

Komata, Makiko ;

Katou, Yuki ;

Clark, Dinah ;

Cole, Kathryn E. ;

De Baere, Elfride ;

Decroos, Christophe ;

Di Donato, Nataliya ;

Ernst, Sarah ;

Francey, Lauren J. ;

Gyftodimou, Yolanda ;

Hirashima, Kyotaro ;

Hullings, Melanie ;

Ishikawa, Yuuichi ;

Jaulin, Christian ;

Kaur, Maninder ;

Kiyono, Tohru ;

Lombardi, Patrick M. ;

Magnaghi-Jaulin, Laura ;

Mortier, Geert R. ;

Nozaki, Naohito ;

Petersen, Michael B. ;

Seimiya, Hiroyuki ;

Siu, Victoria M. ;

Suzuki, Yutaka ;

Takagaki, Kentaro ;

Wilde, Jonathan J. ;

Willems, Patrick J. ;

Prigent, Claude ;

Gillessen-Kaesbach, Gabriele ;

Christianson, David W. ;

Kaiser, Frank J. ;

Jackson, Laird G. ;

Hirota, Toru ;

Krantz, Ian D. ;

Shirahige, Katsuhiko .

NATURE, 2012, 489 (7415) :313-+

[8] RAD21 Mutations Cause a Human Cohesinopathy [J].

Deardorff, Matthew A. ;

Wilde, Jonathan J. ;

Albrecht, Melanie ;

Dickinson, Emma ;

Tennstedt, Stephanie ;

Braunholz, Diana ;

Moennich, Maren ;

Yan, Yuqian ;

Xu, Weizhen ;

Concepcion Gil-Rodriguez, Maria ;

Clark, Dinah ;

Hakonarson, Hakon ;

Halbach, Sara ;

Michelis, Laura Daniela ;

Rampuria, Abhinav ;

Rossier, Eva ;

Spranger, Stephanie ;

Van Maldergem, Lionel ;

Lynch, Sally Ann ;

Gillessen-Kaesbach, Gabriele ;

Luedecke, Hermann-Josef ;

Ramsay, Robert G. ;

McKay, Michael J. ;

Krantz, Ian D. ;

Xu, Huiling ;

Horsfield, Julia A. ;

Kaiser, Frank J. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2012, 90 (06) :1014-1027

[9] Molecular characterization of a mosaic NIPBL deletion in a Cornelia de Lange patient with severe phenotype [J].

Gervasini, Cristina ;

Parenti, Ilaria ;

Picinelli, Chiara ;

Azzollini, Jacopo ;

Masciadri, Maura ;

Cereda, Anna ;

Selicorni, Angelo ;

Russo, Silvia ;

Finelli, Palma ;

Larizza, Lidia .

EUROPEAN JOURNAL OF MEDICAL GENETICS, 2013, 56 (03) :138-143

[10] NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations [J].

Gillis, LA ;

McCallum, J ;

Kaur, M ;

DeScipio, C ;

Yaeger, D ;

Mariani, A ;

Kline, AD ;

Li, HH ;

Devoto, M ;

Jackson, LG ;

Krantz, ID .

AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (04) :610-623

← 1 2 →