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

Radhakrishna, U.; Bornholdt, D.; Scott, Hamish Steele; Patel, U. C.; Rossier, Colette; Engel, H.; Bottani, Armand; Chandal, D.; Blouin, Jean-Louis; Solanki, J. V.; Grzeschik, K. H.; Antonarakis, Stylianos

doi:10.1086/302557

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Title		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
Authors		Radhakrishna, U. Bornholdt, D. Scott, Hamish Steele Patel, U. C. Rossier, Colette Engel, H. Bottani, Armand Chandal, D. Blouin, Jean-Louis Solanki, J. V. Grzeschik, K. H. Antonarakis, Stylianos show all authors [1 - 12]
Published in		American Journal of Human Genetics. 1999, vol. 65, no. 3, p. 645-655
Abstract		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.
Keywords		Amino Acid Sequence — Base Sequence — Chromosomes, Human, Pair 7/genetics — Codon/genetics — DNA Mutational Analysis — DNA-Binding Proteins/genetics/ metabolism — Exons/genetics — Family Health — Female — Genes, Dominant/ genetics — Genotype — Humans — India — Kruppel-Like Transcription Factors — Linkage (Genetics)/genetics — Male — Molecular Sequence Data — Mutation — Nerve Tissue Proteins — Pedigree — Phenotype — Polydactyly/ genetics/physiopathology — Polymorphism, Genetic/genetics — Repressor Proteins — Syndrome — Transcription Factors/genetics/ metabolism — Xenopus Proteins
Identifiers		DOI: 10.1086/302557 PMID: 10441570
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377970/pdf/10441570.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		RADHAKRISHNA, U. et al. 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. In: American Journal of Human Genetics, 1999, vol. 65, n° 3, p. 645-655. doi: 10.1086/302557 https://archive-ouverte.unige.ch/unige:8979