TY - JOUR
T1 - A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree
AU - Marconi, Caterina
AU - Binello, Paolo Brunamonti
AU - Badiali, Giovanni
AU - Caci, Emanuela
AU - Cusano, Roberto
AU - Garibaldi, Joseph
AU - Pippucci, Tommaso
AU - Merlini, Alberto
AU - Marchetti, Claudio
AU - Rhoden, Kerry J.
AU - Galietta, Luis J V
AU - Lalatta, Faustina
AU - Balbi, Paolo
AU - Seri, Marco
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
KW - anoctamin 5
KW - calcium-activated chloride channel
KW - gnathodiaphyseal dysplasia
KW - jawbone disease
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U2 - 10.1038/ejhg.2012.224
DO - 10.1038/ejhg.2012.224
M3 - Article
C2 - 23047743
AN - SCOPUS:84886939212
VL - 21
SP - 613
EP - 619
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 6
ER -