title: PDCD10 gene mutations in multiple cerebral cavernous malformations.
abstract: Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, intracerebral haemorrhages, and focal neurological deficits. Familial form shows an autosomal dominant pattern of inheritance with incomplete penetrance and variable clinical expression. Three genes have been identified causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3. Aim of this study is to report additional PDCD10/CCM3 families poorly described so far which account for 10-15% of hereditary cerebral cavernous malformations. Our group investigated 87 consecutive Italian affected individuals (i.e. positive Magnetic Resonance Imaging) with multiple/familial CCM through direct sequencing and Multiplex Ligation-Dependent Probe Amplification (MLPA) analysis. We identified mutations in over 97.7% of cases, and PDCD10/CCM3 accounts for 13.1%. PDCD10/CCM3 molecular screening revealed four already known mutations and four novel ones. The mutated patients show an earlier onset of clinical manifestations as compared to CCM1/CCM2 mutated patients. The study of further families carrying mutations in PDCD10/CCM3 may help define a possible correlation between genotype and phenotype; an accurate clinical follow up of the subjects would help define more precisely whether mutations in PDCD10/CCM3 lead to a characteristic phenotype.
authors.affiliation: Department of Laboratory Medicine, Medical Genetics Unit - Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Maria Sole
authors.initials: MS
authors.lastname: Cigoli
authors.affiliation: Department of Laboratory Medicine, Medical Genetics Unit - Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Avemaria
authors.affiliation: Department of Laboratory Medicine, Medical Genetics Unit - Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: De Benedetti
authors.affiliation: Department of Laboratory Medicine, Medical Genetics Unit - Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Giovanni P
authors.initials: GP
authors.lastname: Gesu
authors.affiliation: Regional Centre for Epilepsy of Childhood and Adolescence - Children's Hospital of Brescia, Brescia, Italy.
authors.forename: Lucio Giordano
authors.initials: LG
authors.lastname: Accorsi
authors.affiliation: Paediatrics & Neonatology Unit, Eastern Liguria Hospital, La Spezia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Parmigiani
authors.affiliation: Paediatrics & Neonatology Unit, Eastern Liguria Hospital, La Spezia, Italy.
authors.forename: Maria Franca
authors.initials: MF
authors.lastname: Corona
authors.affiliation: Neurosurgery Unit, G.Gaslini Institute, Genova, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mosca
authors.affiliation: Child Neurology and Psychiatry Unit - AUSL Bologna, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Giovannini
authors.affiliation: Department of Human Motor Sciences and Neuromuscular Diseases Unit, Institute of Aging, "G. D'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Notturno
authors.affiliation: Department of Human Motor Sciences and Neuromuscular Diseases Unit, Institute of Aging, "G. D'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Fausta
authors.initials: F
authors.lastname: Ciccocioppo
authors.affiliation: Neurology Unit- AUSL Bologna - Bellaria Pizzardi Hospital, Bologna, Italy.
authors.forename: Lilia
authors.initials: L
authors.lastname: Volpi
authors.affiliation: Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Estienne
authors.affiliation: Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.affiliation: Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Antenora
authors.affiliation: Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: Leda
authors.initials: L
authors.lastname: Bilo
authors.affiliation: Child Neuropsychiatry - A.O.U United Hospitals of Ancona, Ancona, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Tavoni
authors.affiliation: Child Neuropsychiatry - A.O.U United Hospitals of Ancona, Ancona, Italy.
authors.forename: Nelia
authors.initials: N
authors.lastname: Zamponi
authors.affiliation: Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Alfei
authors.affiliation: Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Baranello
authors.affiliation: Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Riva
authors.affiliation: Department of Laboratory Medicine, Medical Genetics Unit - Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins