A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree

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...

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2013-06, Vol.21 (6), p.613-619
Main Authors: Marconi, Caterina, Brunamonti Binello, Paolo, Badiali, Giovanni, Caci, Emanuela, Cusano, Roberto, Garibaldi, Joseph, Pippucci, Tommaso, Merlini, Alberto, Marchetti, Claudio, Rhoden, Kerry J, Galietta, Luis J V, Lalatta, Faustina, Balbi, Paolo, Seri, Marco
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Amino Acid Sequence
Anions - metabolism
Anoctamins
Base Sequence
Biological Transport
Bone dysplasia
Bones
Calcium - metabolism
Calcium channels
Calcium chloride
Chloride
Chloride channels (calcium-gated)
Chloride Channels - chemistry
Chloride Channels - genetics
Cysteine
Dysplasia
Dystrophy
Family
Female
Fractures
Genetics
HEK293 Cells
Humans
Italy
Male
Missense mutation
Molecular Sequence Data
Muscular dystrophy
Mutation
Mutation, Missense - genetics
Osteogenesis Imperfecta - diagnostic imaging
Osteogenesis Imperfecta - genetics
Pedigree
Phenotype
Proteins
Radiography
Sequence Alignment
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Description
Summary: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.
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2012.224