title: De novo 15q21.1q21.2 deletion identified through FBN1 MLPA and refined by 244K array-CGH in a female teenager with incomplete Marfan syndrome.
abstract: Interstitial deletions involving the 15q21.1 band are very rare. Only 4 of these cases have been studied using molecular cytogenetic techniques in order to confirm the deletion of the whole FBN1 gene. The presence of clinical features of the Marfan syndrome (MFS) spectrum associated with mental retardation has been described in only 2/4 patients. Here we report on a 16-year-old female referred for suspicion of MFS (positive thumb and wrist sign, scoliosis, joint hyperlaxity, high-arched palate with dental crowding, dysmorphism, mitral insufficiency with dystrophic valve, striae). She had therefore 3 minor criteria according to the Ghent nosology. She also had speech disabilities but could follow normal school training. Direct sequencing of the FBN1, TGFBR1 and TGFBR2 genes was negative. MLPA revealed a genomic deletion of the whole FBN1 gene, confirmed by loss of heterozygosity of maternal alleles for several microsatellite markers surrounding the FBN1 gene. The deletion was confirmed by FISH using a FBN1 probe and was not found in the parents. Array-CGH permitted to define a 2.97 Mb deletion, which was the smallest 15q microdeletion including FBN1. Contrary to the other published observations, our proband does not exhibit mental retardation, but neuropsychological evaluations revealed an attention deficit as well as a deficit in information-processing speed. Haploinsufficiency of FBN1 is likely to contribute to the presence of MFS features. However, attenuated features could be explained because disturbances of TGF-beta signalling associated with FBN1 mutations do not exert full phenotypic effect through simple haploinsufficiency. Phenotypic variability in other patients with interstitial deletions including 15q21.1 band may reflect differences in deletion size and/or cys/trans modifying factors.
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU Dijon, Université de Bourgogne, Dijon F-21000, France. laurence.faivre@chu-dijon.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Philippe
authors.initials: P
authors.lastname: Khau Van Kien
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ruiz-Pallares
authors.forename: Corinne
authors.initials: C
authors.lastname: Baudoin
authors.forename: Aurélie
authors.initials: A
authors.lastname: Plancke
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Wolf
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Edith
authors.initials: E
authors.lastname: Durand
authors.forename: Delphine
authors.initials: D
authors.lastname: Minot
authors.forename: Véronique
authors.initials: V
authors.lastname: Dulieu
authors.forename: Jean-Damien
authors.initials: JD
authors.lastname: Metaizeau
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.forename: Fanny
authors.initials: F
authors.lastname: Coron
authors.forename: Samuel
authors.initials: S
authors.lastname: Bidot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Francine
authors.initials: F
authors.lastname: Mugneret
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D015342:DNA Probes; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D054392:Adipokines
chemical_list: D015342:DNA Probes; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines