Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures

Autor: Michel Francoise, Patrick Callier, Steven A. Vokes, Susanne Kjaergaard, Laurence Duplomb, Thomas Lee Dahm, Julien Thevenon, Nicole Monnier, Marie Hélène Aubriot-Lorton, Frédéric Huet, Tara Montgomery, Haley O. Tucker, Clémence Ragon, Nathalie Marle, Katherine Neas, Francine Mugneret, Pierre-Simon Jouk, Joël Lunardi, Klaus Dieterich, Laurence Faivre, Christel Thauvin-Robinet, Anne Laure Mosca-Boidron, Joanne Dixon
Přispěvatelé: Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Laboratoire de cytogénétique (CHU de Dijon), Centre de génétique et Centre de référence maladies rares et anomalies du développement et syndromes malformatifs du Centre Est, Département de Génétique et Procréation UF-Hôpital Couple Enfant de Grenoble-CHU Grenoble, Service de pédiatrie, Centre Hospitalier Wiliam Morey, Northern Genetics Service, Newcastle University [Newcastle], Department of Clinical Genetic, Rigshospitalet [Copenhagen], Central and Southern Regional Genetic Services, Wellington Hospital Private, Department of Pediatrics, Nordsjællands Hospital - Hillerød, Service de pédiatrie (CHU de Dijon), Service de Pathologie [CHU de Dijon], Section of Molecular Cell & Developmental Biology, Institute for Cellular and Molecular Biology-University of Texas at Austin [Austin], Graduate Program in Cell and Molecular Biology, University of Texas at Austin [Austin], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Chalon-sur-Saône William Morey, Department of Clinical Genetics [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Texas at Austin [Austin]- Institute for Cellular and Molecular Biology, Roux-Buisson, Nathalie
Rok vydání: 2014
Předmět:
Male
Pathology
medicine.medical_specialty
Contracture
[SDV]Life Sciences [q-bio]
Locus (genetics)
FOXP1
Biology
Mice
distal limb contractures
symbols.namesake
Exon
EIF4E3
Intellectual disability
Genetics
medicine
Animals
Humans
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
3p141p13 microdeletion
Genetics (clinical)
Arthrogryposis
Chromosome Aberrations
Mice
Knockout
Sanger sequencing
Comparative Genomic Hybridization
[ SDV ] Life Sciences [q-bio]
Extremities
Forkhead Transcription Factors
Syndrome
Microdeletion syndrome
medicine.disease
Blepharophimosis
Phenotype
Repressor Proteins
[SDV] Life Sciences [q-bio]
array-CGH
[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
symbols
Female
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Chromosomes
Human
Pair 3
France
Carrier Proteins
intronic regulatory sequence
Zdroj: American Journal of Medical Genetics Part A
American Journal of Medical Genetics Part A, Wiley, 2014, pp.3027-34. 〈10.1002/ajmg.a.36751〉
American Journal of Medical Genetics Part A, Wiley, 2014, pp.3027-34. ⟨10.1002/ajmg.a.36751⟩
ISSN: 1552-4825
1552-4833
Popis: International audience; 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 micro-deletion. 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.
Databáze: OpenAIRE
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