Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability

被引：22

作者：

Callier, P. ^{[1
,2
]}

Aral, B. ^{[2
,3
,4
]}

Hanna, N.

Lambert, S. ^{[2
,3
,4
]}

Dindy, H. ^{[2
]}

Ragon, C. ^{[1
]}

Payet, M. ^{[2
]}

Collod-Beroud, G. ^{[5
]}

Carmignac, V.

Delrue, M. A. ^{[6
]}

Goizet, C. ^{[6
]}

Philip, N. ^{[7
]}

Busa, T. ^{[7
]}

Dulac, Y. ^{[8
]}

Missotte, I. ^{[9
]}

Sznajer, Y. ^{[10
]}

Toutain, A. ^{[11
]}

Francannet, C. ^{[12
]}

Megarbane, A. ^{[13
]}

Julia, S. ^{[14
]}

Edouard, T. ^{[15
]}

Sarda, P. ^{[16
]}

Amiel, J. ^{[17
]}

Lyonnet, S. ^{[17
]}

Cormier-Daire, V. ^{[17
]}

Gilbert, B. ^{[18
]}

Jacquette, A. ^{[19
]}

Heron, D. ^{[19
]}

Collignon, P. ^{[20
]}

Lacombe, D. ^{[6
]}

Morice-Picard, F. ^{[6
]}

Jouk, P. S. ^{[21
]}

Cusin, V. ^{[22
]}

Willems, M. ^{[17
]}

Sarrazin, E. ^{[23
]}

Amarof, K. ^{[23
]}

Coubes, C. ^{[16
]}

Addor, M. C. ^{[24
]}

Journel, H. ^{[25
]}

Colin, E. ^{[26
]}

Van Kien, P. Khau ^{[27
]}

Baumann, C. ^{[28
]}

Leheup, B. ^{[29
]}

Martin- Coignard, D. ^{[30
]}

Doco-Fenzy, M. ^{[31
]}

Goldenberg, A. ^{[32
]}

Plessis, G. ^{[33
]}

Thevenon, J. ^{[34
]}

Pasquier, L. ^{[35
]}

Odent, S. ^{[35
]}

机构：

[1] Plateau Tech Biol, Cytogenet Serv, Dijon, France

[2] Univ Bourgogne, Equipe GAD, EA 4271, Dijon, France

[3] Plateau Tech Biol, Lab Biol Mol, Dijon, France

[4] Hop Ambroise Pare, AP HP, Lab Biochim & Genet Mol, Boulogne, France

[5] INSERM, UMR S 910, F-13000 Marseille, France

[6] CHU Bordeaux & Univ Bordeaux, Dept Genet, Bordeaux, France

[7] Assistance Publ Hop Marseille, Dept Genet, Marseille, France

[8] Serv Cardiol, Toulouse, France

[9] Ctr Hosp Terr, Serv Pediatrie, New Caledonia, France

[10] Serv Genet, Louvain, France

[11] Serv Genet, Tours, France

[12] Serv Genet, Clermont Ferrand, France

[13] Univ St Joseph, Fac Med, Unite Genet Med, Beirut, Lebanon

[14] Serv Genet, Toulouse, France

[15] Serv Pediat, Toulouse, France

[16] Serv Genet, Montpellier, France

[17] Hop Necker Enfants Malad, Dept Genet, Paris, France

[18] Inst Med Genet, Poitiers, France

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

[20] CH Font Pre, Serv Genet Med, Toulon, France

[21] Serv Genet Med, Grenoble, France

[22] Hop Bichat Claude Bernard, Ctr Reference Malad Marfan, Paris, France

[23] Ctr Reference Caraibeen Malad Rares Neurolog & Ne, La Martinique, France

[24] Ctr Hosp Vaudois, Serv Genet Med, Lausanne, Switzerland

[25] Serv Genet Med, Vannes, France

[26] Dept Genet, Angers, France

[27] Serv Biol Mol, Montpellier, France

[28] Hop Robert Debre, Serv Genet Med, F-75019 Paris, France

[29] Dept Genet, Nancy, France

[30] Serv Genet Med, Le Mans, France

[31] CHU Reims EA3801 SFR Cap Sante, Ctr Reference Malad Rares Anomalies, Dept Genet, Reims, France

[32] Dept Genet, Rouen, France

[33] Serv Genet, Caen, France

[34] Hop Enfants, Ctr Genet & Ctr Reference Anomalies Dev, Dijon, France

[35] Ctr Reference Anomalies Dev, Serv Genet Med, Rennes, France

[36] Ctr Invest Clin Epidemiol Clin, Dijon, France

来源：

CLINICAL GENETICS | 2013年 / 84卷 / 06期

关键词：

FBN1; gene; intellectual disability; Lujan-Fryns; marfanoid syndromes; MED12; submicroscopic chromosomal rearrangements; SHPRINTZEN-GOLDBERG-SYNDROME; LINKED MENTAL-RETARDATION; 3Q29 MICRODELETION SYNDROME; LUJAN-FRYNS-SYNDROME; MESSENGER-RNA DECAY; DIAGNOSTIC-CRITERIA; ARRAY-CGH; I FIBRILLINOPATHIES; MUTATION DETECTION; MISSENSE MUTATION;

D O I：

10.1111/cge.12094

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent (R); Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.

引用

页码：507 / 521

页数：15

共 71 条

[1] FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited [J].

Ades, LC ;

Sullivan, K ;

Biggin, A ;

Haan, EA ;

Brett, M ;

Holman, KJ ;

Dixon, J ;

Robertson, S ;

Holmes, AD ;

Rogers, J ;

Bennetts, B .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2006, 140A (10) :1047-1058

[2]

ALLEN RC, 1992, AM J HUM GENET, V51, P1229

[3]

Arbustini Eloisa, 2005, Hum Mutat, V26, P494, DOI 10.1002/humu.9377

[4] Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication [J].

Ballif, Blake C. ;

Theisen, Aaron ;

Coppinger, Justine ;

Gowans, Gordon C. ;

Hersh, Joseph H. ;

Madan-Khetarpal, Suneeta ;

Schmidt, Karen R. ;

Tervo, Raymond ;

Escobar, Luis F. ;

Friedrich, Christopher A. ;

McDonald, Marie ;

Campbell, Lindsey ;

Ming, Jeffrey E. ;

Zackai, Elaine H. ;

Bejjani, Bassem A. ;

Shaffer, Lisa G. .

MOLECULAR CYTOGENETICS, 2008, 1 (1)

[5]

Biggin Andrew, 2004, Hum Mutat, V23, P99, DOI 10.1002/humu.9207

[6] The mediator of RNA polymerase II [J].

Blazek, E ;

Mittler, G ;

Meisterernst, M .

CHROMOSOMA, 2005, 113 (08) :399-408

[7] The FBN1 (R2726W) mutation is not fully penetrant [J].

Buoni, S ;

Zannolli, R ;

Macucci, F ;

Ansaldi, S ;

Grasso, M ;

Arbustini, E ;

Fois, A .

ANNALS OF HUMAN GENETICS, 2004, 68 :633-638

[8] Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphlism database [J].

Collod-Béroud, G ;

Le Bourdelles, S ;

Ades, L ;

Ala-Kokko, L ;

Booms, P ;

Boxer, M ;

Child, A ;

Comeglio, P ;

De Paepe, A ;

Hyland, JC ;

Holman, K ;

Kaitila, I ;

Loeys, B ;

Matyas, G ;

Nuytinck, L ;

Peltonen, L ;

Rantamaki, T ;

Robinson, P ;

Steinmann, B ;

Junien, C ;

Béroud, C ;

Boileau, C .

HUMAN MUTATION, 2003, 22 (03) :199-208

[9]

Comeglio P, 2001, Hum Mutat, V18, P251, DOI 10.1002/humu.1181

[10]

Comeglio Paolo, 2007, Hum Mutat, V28, P928, DOI 10.1002/humu.9505

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