title: Small deletion at the 7q21.2 locus in a CCM family detected by real-time quantitative PCR.
abstract: Cerebral cavernous malformations (CCMs) represent a common autosomal dominant disorder that predisposes patients to haemorrhagic strokes and focal neurological signs. About 56% of the hereditary forms of CCMs have been so far associated with mutations in the KRIT1 (Krev Interaction Trapped 1) gene, located at 7q21.2 (CCM1 locus). We described the complete loss of 7q21.2 locus encompassing the KRIT1 gene and 4 flanking genes in a CCM family by using a dense set of 12 microsatellite markers. The complete loss of the maternal copy of KRIT1 gene region was confirmed by Real-Time Quantitative Polymerase Chain Reaction (RT-QPCR) and the same approach was used for expression analysis. Additional RT-QPCR analysis showed the extension of the deletion, for a total of 700 kb, to the adjacent downstream and upstream-located genes, MTERF, AKAP9, CYP51A1, as well as a partial loss of the ANKIB1 gene. Here we report the molecular characterization of an interstitial small genomic deletion of the 7q21.2 region in a CCMs affected family, encompassing the KRIT1 gene. Our findings confirm the loss of function mechanism for the already known CCM1 locus, without any evident involvement of the other deleted genes. Moreover, our investigations highlight the usefulness of the RT-QPCR to the molecular characterization of the breakpoints genomic deletions and to the identification of internal deleted genes involved in the human genetic diseases.
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo (FG), Italy. l.muscarella@operapadrepio.it
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Muscarella
authors.forename: Vito
authors.initials: V
authors.lastname: Guarnieri
authors.forename: Michelina
authors.initials: M
authors.lastname: Coco
authors.forename: Serena
authors.initials: S
authors.lastname: Belli
authors.forename: Paola
authors.initials: P
authors.lastname: Parrella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pulcrano
authors.forename: Domenico
authors.initials: D
authors.lastname: Catapano
authors.forename: Vincenzo A
authors.initials: VA
authors.lastname: D'Angelo
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Leonardo
authors.initials: L
authors.lastname: D'Agruma
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics; D002648:Child; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D006392:Hemangioma, Cavernous / Q000235:genetics*; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics*; D000075927:KRIT1 Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins
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