title: Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability.
abstract: 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 families.
authors.affiliation: Service de Cytogénétique, Plateau technique de Biologie, CHU, Dijon, France; Equipe GAD, EA 4271, Université de Bourgogne, Dijon, France.
authors.forename: P
authors.initials: P
authors.lastname: Callier
authors.forename: B
authors.initials: B
authors.lastname: Aral
authors.forename: N
authors.initials: N
authors.lastname: Hanna
authors.forename: S
authors.initials: S
authors.lastname: Lambert
authors.forename: H
authors.initials: H
authors.lastname: Dindy
authors.forename: C
authors.initials: C
authors.lastname: Ragon
authors.forename: M
authors.initials: M
authors.lastname: Payet
authors.forename: G
authors.initials: G
authors.lastname: Collod-Beroud
authors.forename: V
authors.initials: V
authors.lastname: Carmignac
authors.forename: M A
authors.initials: MA
authors.lastname: Delrue
authors.forename: C
authors.initials: C
authors.lastname: Goizet
authors.forename: N
authors.initials: N
authors.lastname: Philip
authors.forename: T
authors.initials: T
authors.lastname: Busa
authors.forename: Y
authors.initials: Y
authors.lastname: Dulac
authors.forename: I
authors.initials: I
authors.lastname: Missotte
authors.forename: Y
authors.initials: Y
authors.lastname: Sznajer
authors.forename: A
authors.initials: A
authors.lastname: Toutain
authors.forename: C
authors.initials: C
authors.lastname: Francannet
authors.forename: A
authors.initials: A
authors.lastname: Megarbane
authors.forename: S
authors.initials: S
authors.lastname: Julia
authors.forename: T
authors.initials: T
authors.lastname: Edouard
authors.forename: P
authors.initials: P
authors.lastname: Sarda
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: B
authors.initials: B
authors.lastname: Gilbert
authors.forename: A
authors.initials: A
authors.lastname: Jacquette
authors.forename: D
authors.initials: D
authors.lastname: Heron
authors.forename: P
authors.initials: P
authors.lastname: Collignon
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: F
authors.initials: F
authors.lastname: Morice-Picard
authors.forename: P S
authors.initials: PS
authors.lastname: Jouk
authors.forename: V
authors.initials: V
authors.lastname: Cusin
authors.forename: M
authors.initials: M
authors.lastname: Willems
authors.forename: E
authors.initials: E
authors.lastname: Sarrazin
authors.forename: K
authors.initials: K
authors.lastname: Amarof
authors.forename: C
authors.initials: C
authors.lastname: Coubes
authors.forename: M C
authors.initials: MC
authors.lastname: Addor
authors.forename: H
authors.initials: H
authors.lastname: Journel
authors.forename: E
authors.initials: E
authors.lastname: Colin
authors.forename: P
authors.initials: P
authors.lastname: Khau Van Kien
authors.forename: C
authors.initials: C
authors.lastname: Baumann
authors.forename: B
authors.initials: B
authors.lastname: Leheup
authors.forename: D
authors.initials: D
authors.lastname: Martin-Coignard
authors.forename: M
authors.initials: M
authors.lastname: Doco-Fenzy
authors.forename: A
authors.initials: A
authors.lastname: Goldenberg
authors.forename: G
authors.initials: G
authors.lastname: Plessis
authors.forename: J
authors.initials: J
authors.lastname: Thevenon
authors.forename: L
authors.initials: L
authors.lastname: Pasquier
authors.forename: S
authors.initials: S
authors.lastname: Odent
authors.forename: P
authors.initials: P
authors.lastname: Vabres
authors.forename: F
authors.initials: F
authors.lastname: Huet
authors.forename: N
authors.initials: N
authors.lastname: Marle
authors.forename: A L
authors.initials: AL
authors.lastname: Mosca-Boidron
authors.forename: F
authors.initials: F
authors.lastname: Mugneret
authors.forename: S
authors.initials: S
authors.lastname: Gauthier
authors.forename: C
authors.initials: C
authors.lastname: Binquet
authors.forename: C
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: G
authors.initials: G
authors.lastname: Jondeau
authors.forename: C
authors.initials: C
authors.lastname: Boileau
authors.forename: L
authors.initials: L
authors.lastname: Faivre
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D049951:X Chromosome Inactivation; D055815:Young Adult
keywords: FBN1 gene; Lujan-Fryns; MED12 gene; intellectual disability; marfanoid syndromes; submicroscopic chromosomal rearrangements