title: A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree.
abstract: Gnathodiaphyseal dysplasia (GDD) is an autosomal dominant syndrome characterized by frequent bone fractures at a young age, bowing of tubular bones and cemento-osseus lesions of the jawbones. Anoctamin 5 (ANO5) belongs to the anoctamin protein family that includes calcium-activated chloride channels. However, recent data together with our own experiments reported here add weight to the hypothesis that ANO5 may not function as calcium-activated chloride channel. By sequencing the entire ANO5 gene coding region and untranslated regions in a large Italian GDD family, we found a novel missense mutation causing the p.Thr513Ile substitution. The mutation segregates with the disease in the family and has never been described in any database as a polymorphism. To date, only two mutations on the same cysteine residue at position 356 of ANO5 amino-acid sequence have been described in GDD families. As ANO5 has also been found to be mutated in two different forms of muscular dystrophy, the finding of this third mutation in GDD adds clues to the role of ANO5 in these disorders.
authors.affiliation: Unità di Genetica Medica, Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, Università di Bologna, Bologna, Italy. marco.seri@unibo.it
authors.forename: Caterina
authors.initials: C
authors.lastname: Marconi
authors.forename: Paolo
authors.initials: P
authors.lastname: Brunamonti Binello
authors.forename: Giovanni
authors.initials: G
authors.lastname: Badiali
authors.forename: Emanuela
authors.initials: E
authors.lastname: Caci
authors.forename: Roberto
authors.initials: R
authors.lastname: Cusano
authors.forename: Joseph
authors.initials: J
authors.lastname: Garibaldi
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pippucci
authors.forename: Alberto
authors.initials: A
authors.lastname: Merlini
authors.forename: Claudio
authors.initials: C
authors.lastname: Marchetti
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Rhoden
authors.forename: Luis J V
authors.initials: LJ
authors.lastname: Galietta
authors.forename: Faustina
authors.initials: F
authors.lastname: Lalatta
authors.forename: Paolo
authors.initials: P
authors.lastname: Balbi
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000838:Anions / Q000378:metabolism; D000075368:Anoctamins; D001483:Base Sequence; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics*; D005190:Family; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007558:Italy; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D016415:Sequence Alignment
chemical_list: C547813:ANO5 protein, human; D000838:Anions; D000075368:Anoctamins; D018118:Chloride Channels; D002118:Calcium