PMID- 10441570
OWN - NLM
STAT- MEDLINE
DCOM- 19991004
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 3
DP  - 1999 Sep
TI  - The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant
      preaxial polydactyly type-IV and postaxial polydactyly type-A/B; No phenotype
      prediction from the position of GLI3 mutations.
PG  - 645-55
AB  - Functional characterization of a gene often requires the discovery of the full
      spectrum of its associated phenotypes. Mutations in the human GLI3 gene have been
      identified in Greig cepalopolysyndactyly, Pallister-Hall syndrome (PHS), and
      postaxial polydactyly type-A (PAP-A). We studied the involvement of GLI3 in
      additional phenotypes of digital abnormalities in one family (UR003) with
      preaxial polydactyly type-IV (PPD-IV), three families (UR014, UR015, and UR016)
      with dominant PAP-A/B (with PPD-A and -B in the same family), and one family with
      PHS. Linkage analysis showed no recombination with GLI3-linked polymorphisms.
      Family UR003 had a 1-nt frameshift insertion, resulting in a truncated protein of
      1,245 amino acids. A frameshift mutation due to a 1-nt deletion was found in
      family UR014, resulting in a truncated protein of 1,280 amino acids. Family UR015
      had a nonsense mutation, R643X, and family UR016 had a missense mutation, G727R, 
      in a highly conserved amino acid of domain 3. The patient with PHS had a nonsense
      mutation, E1147X. These results add two phenotypes to the phenotypic spectrum
      caused by GLI3 mutations: the combined PAP-A/B and PPD-IV. These mutations do not
      support the suggested association between the mutations in GLI3 and the resulting
      phenotypes. We propose that all phenotypes associated with GLI3 mutations be
      called "GLI3 morphopathies," since the phenotypic borders of the resulting
      syndromes are not well defined and there is no apparent genotype-phenotype
      correlation.
FAU - Radhakrishna, U
AU  - Radhakrishna U
AD  - Division of Medical Genetics, University of Geneva Medical School, Geneva,
      Switzerland.
FAU - Bornholdt, D
AU  - Bornholdt D
FAU - Scott, H S
AU  - Scott HS
FAU - Patel, U C
AU  - Patel UC
FAU - Rossier, C
AU  - Rossier C
FAU - Engel, H
AU  - Engel H
FAU - Bottani, A
AU  - Bottani A
FAU - Chandal, D
AU  - Chandal D
FAU - Blouin, J L
AU  - Blouin JL
FAU - Solanki, J V
AU  - Solanki JV
FAU - Grzeschik, K H
AU  - Grzeschik KH
FAU - Antonarakis, S E
AU  - Antonarakis SE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Codon)
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 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Xenopus Proteins)
RN  - 0 (Zinc Finger Protein Gli3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Chromosomes, Human, Pair 7/genetics
MH  - Codon/genetics
MH  - DNA Mutational Analysis
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Exons/genetics
MH  - Family Health
MH  - Female
MH  - Genes, Dominant/*genetics
MH  - Genetic Linkage/genetics
MH  - Genotype
MH  - Humans
MH  - India
MH  - Kruppel-Like Transcription Factors
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - *Nerve Tissue Proteins
MH  - Pedigree
MH  - Phenotype
MH  - Polydactyly/*genetics/physiopathology
MH  - Polymorphism, Genetic/genetics
MH  - *Repressor Proteins
MH  - Syndrome
MH  - Transcription Factors/genetics/*metabolism
MH  - *Xenopus Proteins
MH  - Zinc Finger Protein Gli3
PMC - PMC1377970
EDAT- 1999/08/12 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/08/12 10:00
PHST- 1999/08/12 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/08/12 10:00 [entrez]
AID - S0002-9297(07)62315-5 [pii]
AID - 10.1086/302557 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Sep;65(3):645-55. doi: 10.1086/302557.