PMID- 10441342
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 9
DP  - 1999 Sep
TI  - Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly
      syndrome.
PG  - 1769-77
AB  - Greig cephalopolysyndactyly syndrome, characterized by craniofacial and limb
      anomalies (GCPS; MIM 175700), previously has been demonstrated to be associated
      with translocations as well as point mutations affecting one allele of the zinc
      finger gene GLI3. In addition to GCPS, Pallister-Hall syndrome (PHS; MIM 146510) 
      and post-axial polydactyly type A (PAP-A; MIM 174200), two other disorders of
      human development, are caused by GLI3 mutations. In order to gain more insight
      into the mutational spectrum associated with a single phenotype, we report here
      the extension of the GLI3 mutation analysis to 24 new GCPS cases. We report the
      identification of 15 novel mutations present in one of the patient's GLI3
      alleles. The mutations map throughout the coding gene regions. The majority are
      truncating mutations (nine of 15) that engender prematurely terminated protein
      products mostly but not exclusively N-terminally to or within the central region 
      encoding the DNA-binding domain. Two missense and two splicing mutations mapping 
      within the zinc finger motifs presumably also interfere with DNA binding. The
      five mutations identified within the protein regions C-terminal to the zinc
      fingers putatively affect additional functional properties of GLI3. In cell
      transfection experiments using fusions of the DNA-binding domain of yeast GAL4 to
      different segments of GLI3, transactivating capacity was assigned to two adjacent
      independent domains (TA(1)and TA(2)) in the C-terminal third of GLI3. Since these
      are the only functional domains affected by three C-terminally truncating
      mutations, we postulate that GCPS may be due either to haploinsufficiency
      resulting from the complete loss of one gene copy or to functional
      haploinsufficiency related to compromised properties of this transcription factor
      such as DNA binding and transactivation.
FAU - Kalff-Suske, M
AU  - Kalff-Suske M
AD  - Medizinisches Zentrum fur Humangenetik, Philipps-Universitat Marburg, D-35037
      Marburg, Germany.
FAU - Wild, A
AU  - Wild A
FAU - Topp, J
AU  - Topp J
FAU - Wessling, M
AU  - Wessling M
FAU - Jacobsen, E M
AU  - Jacobsen EM
FAU - Bornholdt, D
AU  - Bornholdt D
FAU - Engel, H
AU  - Engel H
FAU - Heuer, H
AU  - Heuer H
FAU - Aalfs, C M
AU  - Aalfs CM
FAU - Ausems, M G
AU  - Ausems MG
FAU - Barone, R
AU  - Barone R
FAU - Herzog, A
AU  - Herzog A
FAU - Heutink, P
AU  - Heutink P
FAU - Homfray, T
AU  - Homfray T
FAU - Gillessen-Kaesbach, G
AU  - Gillessen-Kaesbach G
FAU - Konig, R
AU  - Konig R
FAU - Kunze, J
AU  - Kunze J
FAU - Meinecke, P
AU  - Meinecke P
FAU - Muller, D
AU  - Muller D
FAU - Rizzo, R
AU  - Rizzo R
FAU - Strenge, S
AU  - Strenge S
FAU - Superti-Furga, A
AU  - Superti-Furga A
FAU - Grzeschik, K H
AU  - Grzeschik KH
LA  - eng
SI  - GENBANK/AJ250408
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GLI3 protein, Xenopus)
RN  - 0 (GLI3 protein, human)
RN  - 0 (Gli3 protein, mouse)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Xenopus Proteins)
RN  - 0 (Zinc Finger Protein Gli3)
SB  - IM
MH  - Animals
MH  - Craniofacial Abnormalities/*genetics
MH  - DNA Mutational Analysis
MH  - DNA-Binding Proteins/*genetics
MH  - Drosophila
MH  - Humans
MH  - Kruppel-Like Transcription Factors
MH  - Limb Deformities, Congenital/*genetics
MH  - *Mutation
MH  - *Nerve Tissue Proteins
MH  - Recombinant Fusion Proteins
MH  - *Repressor Proteins
MH  - Sequence Deletion
MH  - Syndrome
MH  - Transcription Factors/*genetics
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - *Xenopus Proteins
MH  - Zinc Finger Protein Gli3
MH  - Zinc Fingers/genetics
EDAT- 1999/08/11 00:00
MHDA- 1999/08/11 00:01
CRDT- 1999/08/11 00:00
PHST- 1999/08/11 00:00 [pubmed]
PHST- 1999/08/11 00:01 [medline]
PHST- 1999/08/11 00:00 [entrez]
AID - ddc180 [pii]
AID - 10.1093/hmg/8.9.1769 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Sep;8(9):1769-77. doi: 10.1093/hmg/8.9.1769.