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

P Callier, B Aral, N Hanna, S Lambert, H Dindy, C Ragon, M Payet, G Collod-Beroud, V Carmignac, MA Delrue, C Goizet, N Philip, T Busa, Y Dulac, I Missotte, Y Sznajer, A Toutain, C Francannet, A Megarbane, S Julia, T Edouard, P Sarda, J Amiel, S Lyonnet, V Cormier-Daire, B Gilbert, A Jacquette, D Heron, P Collignon, D Lacombe, F Morice-Picard, PS Jouk, V Cusin, M Willems, E Sarrazin, K Amarof, C Coubes, MC Addor, H Journel, E Colin, P Khau Van Kien, C Baumann, B Leheup, D Martin- Coignard, M Doco-Fenzy, A Goldenberg, G Plessis, J Thevenon, L Pasquier, S Odent, P Vabres, F Huet, N Marle, AL Mosca- Boidron, F Mugneret, S Gauthier, C Binquet, C Thauvin-Robinet, G Jondeau, C Boileau, L Faivre
Clin Genet. 2013-03-18; 84(6): 507-521
DOI: 10.1111/CGE.12094

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1. Clin Genet. 2013 Dec;84(6):507-21. doi: 10.1111/cge.12094. Epub 2013 Mar 18.

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

Callier P(1), Aral B, Hanna N, Lambert S, Dindy H, Ragon C, Payet M,
Collod-Beroud G, Carmignac V, Delrue MA, Goizet C, Philip N, Busa T, Dulac Y,
Missotte I, Sznajer Y, Toutain A, Francannet C, Megarbane A, Julia S, Edouard T,
Sarda P, Amiel J, Lyonnet S, Cormier-Daire V, Gilbert B, Jacquette A, Heron D,
Collignon P, Lacombe D, Morice-Picard F, Jouk PS, Cusin V, Willems M, Sarrazin E,
Amarof K, Coubes C, Addor MC, Journel H, Colin E, Khau Van Kien P, Baumann C,
Leheup B, Martin-Coignard D, Doco-Fenzy M, Goldenberg A, Plessis G, Thevenon J,
Pasquier L, Odent S, Vabres P, Huet F, Marle N, Mosca-Boidron AL, Mugneret F,
Gauthier S, Binquet C, Thauvin-Robinet C, Jondeau G, Boileau C, Faivre L.

Author information:
(1)Service de Cytogénétique, Plateau technique de Biologie, CHU, Dijon, France;
Equipe GAD, EA 4271, Université de Bourgogne, Dijon, France.

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®; 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

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DOI: 10.1111/cge.12094
PMID: 23506379 [Indexed for MEDLINE]

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