title: Search for a gene responsible for Floating-Harbor syndrome on chromosome 12q15q21.1.
abstract: Floating-Harbor syndrome (FHS) is characterized by characteristic facial dysmorphism, short stature with delayed bone age, and expressive language delay. To date, the gene(s) responsible for FHS is (are) unknown and the diagnosis is only made on the basis of the clinical phenotype. The majority of cases appeared to be sporadic but rare cases following autosomal dominant inheritance have been reported. We identified a 4.7 Mb de novo 12q15-q21.1 microdeletion in a patient with FHS and intellectual deficiency. Pangenomic 244K array-CGH performed in a series of 12 patients with FHS failed to identify overlapping deletions. We hypothesized that FHS is caused by haploinsufficiency of one of the 19 genes or predictions located in the deletion found in our index patient. Since none of them appeared to be good candidate gene by their function, a high-throughput sequencing approach of the region of interest was used in eight FHS patients. No pathogenic mutation was found in these patients. This approach failed to identify the gene responsible for FHS, and this can be explained by at least four reasons: (i) our index patient could be a phenocopy of FHS; (ii) the disease may be clinically heterogeneous (since the diagnosis relies exclusively on clinical features), (iii) these could be genetic heterogeneity of the disease, (iv) the patient could carry a mutation in a gene located elsewhere. Recent descriptions of patients with 12q15-q21.1 microdeletions argue in favor of the phenocopy hypothesis.
authors.affiliation: Equipe GAD, IFR Santé-STIC, Université de Bourgogne, Dijon, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Lopez
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
authors.forename: Armand
authors.initials: A
authors.lastname: Bottani
authors.forename: Sandy
authors.initials: S
authors.lastname: Lambert
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Bérénice
authors.initials: B
authors.lastname: Doray
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Lucie
authors.initials: L
authors.lastname: Gueneau
authors.forename: Laurence
authors.initials: L
authors.lastname: Duplomb
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Bernard
authors.initials: B
authors.lastname: Aral
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology*; D057895:Haploinsufficiency / Q000235:genetics; D006345:Heart Septal Defects, Ventricular / Q000235:genetics* / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010641:Phenotype; D017384:Sequence Deletion / Q000235:genetics*