title: A novel syndrome of cerebral cavernous malformation and Greig cephalopolysyndactyly. Laboratory investigation.
abstract: OBJECTIVE
  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.
authors.affiliation: Program on Neurogenetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bilguvar
authors.forename: Mohamad
authors.initials: M
authors.lastname: Bydon
authors.forename: Fatih
authors.initials: F
authors.lastname: Bayrakli
authors.forename: A Gulhan
authors.initials: AG
authors.lastname: Ercan-Sencicek
authors.forename: Yasar
authors.initials: Y
authors.lastname: Bayri
authors.forename: Christopher
authors.initials: C
authors.lastname: Mason
authors.forename: Michael L
authors.initials: ML
authors.lastname: DiLuna
authors.forename: Margretta
authors.initials: M
authors.lastname: Seashore
authors.forename: Richard
authors.initials: R
authors.lastname: Bronen
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Matthew
authors.initials: M
authors.lastname: State
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics; D002675:Child, Preschool; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D000074290:Zinc Finger Protein Gli3
chemical_list: C502544:CCM2 protein, human; D002352:Carrier Proteins; C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3; D004247:DNA