TY - JOUR
T1 - A novel syndrome of cerebral cavernous malformation and Greig cephalopolysyndactyly
T2 - Laboratory investigation
AU - Bilguvar, Kaya
AU - Bydon, Mohamad
AU - Bayrakli, Fatih
AU - Ercan-Sencicek, A. Gulhan
AU - Bayri, Yasar
AU - Mason, Christopher
AU - DiLuna, Michael L.
AU - Seashore, Margretta
AU - Bronen, Richard
AU - Lifton, Richard P.
AU - State, Matthew
AU - Gunel, Murat
PY - 2007/12
Y1 - 2007/12
N2 - Object. Greig cephalopolysyndactyly syndrome (GCPS) is one of a spectrum of overlapping clinical syndromes resulting from mutations in the gene GLI3 on chromosome 7p. Cerebral cavernous malformation (CCM) is caused by mutations in three distinct genes, including Malcavernin (CCM2), which also maps to chromosome 7p and is located 2.8 Mbp from GLI3. The authors describe a new syndrome that combines the vascular lesions characteristic of CCM with the hallmarks of GCPS, including polydactyly, hypertelorism, and developmental delay. Methods. The authors used high-resolution array-based comparative genome hybridization (CGH) analysis to characterize the 3 million-bp deletion on chromosome 7 that accounts for this novel clinical presentation. A 4-year-old girl presented with polydactyly, hypertelorism, and developmental delay and was also found to have multiple CCMs after suffering a seizure. Results. Genetic analysis using array-based CGH revealed a deletion affecting multiple genes in the 7p14-13 locus, the interval that includes both CCM2 and GLI3. Quantitative real-time polymerase chain reaction (RT-PCR) on genomic DNA confirmed this genomic lesion. Conclusions. A novel syndrome, combining features of CCM and GCPS, can be added to the group of entities that result from deleterious genetic variants involving GLI3, including GCPS, acrocallosal syndrome, Pallister-Hall syndrome, and contiguous gene syndrome. The deletion responsible for this new entity can be easily detected using either array-based chromosomal analysis or quantitative RT-PCR.
AB - Object. Greig cephalopolysyndactyly syndrome (GCPS) is one of a spectrum of overlapping clinical syndromes resulting from mutations in the gene GLI3 on chromosome 7p. Cerebral cavernous malformation (CCM) is caused by mutations in three distinct genes, including Malcavernin (CCM2), which also maps to chromosome 7p and is located 2.8 Mbp from GLI3. The authors describe a new syndrome that combines the vascular lesions characteristic of CCM with the hallmarks of GCPS, including polydactyly, hypertelorism, and developmental delay. Methods. The authors used high-resolution array-based comparative genome hybridization (CGH) analysis to characterize the 3 million-bp deletion on chromosome 7 that accounts for this novel clinical presentation. A 4-year-old girl presented with polydactyly, hypertelorism, and developmental delay and was also found to have multiple CCMs after suffering a seizure. Results. Genetic analysis using array-based CGH revealed a deletion affecting multiple genes in the 7p14-13 locus, the interval that includes both CCM2 and GLI3. Quantitative real-time polymerase chain reaction (RT-PCR) on genomic DNA confirmed this genomic lesion. Conclusions. A novel syndrome, combining features of CCM and GCPS, can be added to the group of entities that result from deleterious genetic variants involving GLI3, including GCPS, acrocallosal syndrome, Pallister-Hall syndrome, and contiguous gene syndrome. The deletion responsible for this new entity can be easily detected using either array-based chromosomal analysis or quantitative RT-PCR.
KW - Cerebral cavernous malformation
KW - Greig cephalopolysyndactyly
KW - Pediatric neurosurgery
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U2 - 10.3171/PED-07/12/495
DO - 10.3171/PED-07/12/495
M3 - Article
C2 - 18154020
AN - SCOPUS:38449098849
SN - 0022-3085
VL - 107
SP - 495
EP - 499
JO - Journal of neurosurgery
JF - Journal of neurosurgery
IS - 6 SUPPL.
ER -