title: Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures.
abstract: Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20-25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 microdeletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1 named hs1149. Sanger sequencing and locus quantification of hs1149, EIF4E3, and FOXP1 in a cohort of 11 French patients affected by DLC appeared normal. In conclusion, we delineate a new microdeletion syndrome involving the 3p14.1p13 locus and associated with DLC and severe developmental delay.
authors.affiliation: Fédération Hospitalo-Universitaire TRANSLAD et Centre de Génétique et Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» du Grand Est, Hôpital d'Enfants, CHU Dijon, Dijon, France; Université de Bourgogne, Dijon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.forename: Nicole
authors.initials: N
authors.lastname: Monnier
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.forename: Klaus
authors.initials: K
authors.lastname: Dieterich
authors.forename: Michel
authors.initials: M
authors.lastname: Francoise
authors.forename: Tara
authors.initials: T
authors.lastname: Montgomery
authors.forename: Susanne
authors.initials: S
authors.lastname: Kjaergaard
authors.forename: Katherine
authors.initials: K
authors.lastname: Neas
authors.forename: Joanne
authors.initials: J
authors.lastname: Dixon
authors.forename: Thomas Lee
authors.initials: TL
authors.lastname: Dahm
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Clémence
authors.initials: C
authors.lastname: Ragon
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Mosca-Boidron
authors.forename: Nathalie
authors.initials: N
authors.lastname: Marle
authors.forename: Laurence
authors.initials: L
authors.lastname: Duplomb
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Aubriot-Lorton
authors.forename: Francine
authors.initials: F
authors.lastname: Mugneret
authors.forename: Steve A
authors.initials: SA
authors.lastname: Vokes
authors.forename: Haley W
authors.initials: HW
authors.lastname: Tucker
authors.forename: Joël
authors.initials: J
authors.lastname: Lunardi
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Pierre Simon
authors.initials: PS
authors.lastname: Jouk
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
mesh_terms: D000818:Animals; D001176:Arthrogryposis / Q000453:epidemiology*; D002352:Carrier Proteins / Q000235:genetics; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003286:Contracture / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005121:Extremities / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; C112661:EIF4EBP3 protein, human; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins
keywords: 3p14.1p13 microdeletion; EIF4E3; FOXP1; array-CGH; distal limb contractures; intronic regulatory sequence