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 700kb, 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.
| Original language | English |
|---|---|
| Article number | 854737 |
| Journal | Journal of Biomedicine and Biotechnology |
| Volume | 2010 |
| DOIs | |
| Publication status | Published - 2010 |
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ASJC Scopus subject areas
- Biotechnology
- Molecular Medicine
- Genetics
- Molecular Biology
- Health, Toxicology and Mutagenesis
Cite this
Small deletion at the 7q21.2 locus in a CCM family detected by Real-Time Quantitative PCR. / Muscarella, Lucia Anna; Guarnieri, Vito; Coco, Michelina; Belli, Serena; Parrella, Paola; Pulcrano, Giuseppe; Catapano, Domenico; D'Angelo, Vincenzo A.; Zelante, Leopoldo; D'Agruma, Leonardo.
In: Journal of Biomedicine and Biotechnology, Vol. 2010, 854737, 2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Small deletion at the 7q21.2 locus in a CCM family detected by Real-Time Quantitative PCR
AU - Muscarella, Lucia Anna
AU - Guarnieri, Vito
AU - Coco, Michelina
AU - Belli, Serena
AU - Parrella, Paola
AU - Pulcrano, Giuseppe
AU - Catapano, Domenico
AU - D'Angelo, Vincenzo A.
AU - Zelante, Leopoldo
AU - D'Agruma, Leonardo
PY - 2010
Y1 - 2010
N2 - 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 700kb, 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.
AB - 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 700kb, 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.
UR - http://www.scopus.com/inward/record.url?scp=77956759127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956759127&partnerID=8YFLogxK
U2 - 10.1155/2010/854737
DO - 10.1155/2010/854737
M3 - Article
C2 - 20798775
AN - SCOPUS:77956759127
VL - 2010
JO - Journal of Biomedicine and Biotechnology
JF - Journal of Biomedicine and Biotechnology
SN - 1110-7243
M1 - 854737
ER -