title: Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2.
abstract: Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF). A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16) or anoctamin (ANO). TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT). The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability.
authors: Neurobiology Group, SISSA, International School for Advanced Studies, Trieste, Italy.
authors: Valentina
authors: V
authors: Cenedese
authors: Institute for Maternal and Child Health, Istituto Di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo" and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors: Massimo
authors: M
authors: Mezzavilla
authors: Institute for Maternal and Child Health, Istituto Di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo" and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors: Anna
authors: A
authors: Morgan
authors: Centro Emofilia e Trombosi, Azienda Ospedaliero-Universitaria Ospedale Policlinico Consorziale "Giovanni XXIII", Bari, Italy.
authors: Renato
authors: R
authors: Marino
authors: Centro Emofilia e Trombosi, Azienda Ospedaliero-Universitaria Ospedale Policlinico Consorziale "Giovanni XXIII", Bari, Italy.
authors: Cosimo Pietro
authors: CP
authors: Ettorre
authors: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, University of Foggia, Foggia, Italy.
authors: Maurizio
authors: M
authors: Margaglione
authors: Institute for Maternal and Child Health, Istituto Di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo" and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors: Paolo
authors: P
authors: Gasparini
authors: Neurobiology Group, SISSA, International School for Advanced Studies, Trieste, Italy.
authors: Anna
authors: A
authors: Menini
mesh_terms: D000328:Adult; D000075368:Anoctamins; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009831:Olfactory Mucosa / Q000378:metabolism / Q000473:pathology; D055696:Olfactory Perception; D017384:Sequence Deletion; D012903:Smell / Q000235:genetics*; D055815:Young Adult; D056729:von Willebrand Disease, Type 3 / Q000235:genetics / Q000503:physiopathology*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: C521849:ANO2 protein, human; D000075368:Anoctamins; D008565:Membrane Proteins; D014841:von Willebrand Factor
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