Limb disorders
Gene: GLI3
PMID: 32591344 (2021) - Variants that likely produce haploinsufficiency are associated with anteriorly orientated (preaxial) polydactyly. Posterior (postaxial) phenotypes are associated with truncating variants in the activator domain, which is also related to a higher risk of corpus callosum agenesis.Created: 1 Jun 2021, 10:16 a.m. | Last Modified: 1 Jun 2021, 10:16 a.m.
Panel Version: 2.41
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
PMID: 31115189 - Umair et al 2019 - report a five generation Pakastani kindred having 12 affected individuals exhibiting nonsyndromic postaxial polydactyly type A condition. Using exome sequencing in the three affected individuals, they identified a novel heterozygous frameshift variant (c.3567_3568insG; p.Ala1190Glyfs*57) in the transcriptional activator (TA2) domain of GLI3. The variant segregates with the disease phenotype in all members of the family. The variant was not observed in the ExAC browser, gnomAD, 1,000 Genomes, Pakistan Genetic Mutation database (Qasim et al., 2018) and in 135 in‐house exomes (Pakistani exomes).Created: 7 Aug 2019, 12:13 p.m. | Last Modified: 7 Aug 2019, 12:13 p.m.
Panel Version: 1.44
Comment on list classification: Keeping this gene green on the Limb disorders panel, although it is also green on the Rare multisystem ciliopathies panel, on advice of Genomics England clinical team.Created: 2 Dec 2018, 10:18 p.m.
Comment when marking as ready: Associated with phenotypes in G2P. Numerous variants reported in these phenotypes.Created: 12 Jul 2016, 7:50 a.m.
Tier 2Created: 17 Jun 2016, 8:04 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Greig cephalopolysyndactyly syndrome 175700; Pallister-Hall syndrome 146510; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; {Hypothalamic hamartomas, somatic} 241800
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: GLI3 were set to 31115189
Publications for gene: GLI3 were set to
Ana Beleza: Tier 2
Gene: gli3 has been classified as Green List (High Evidence).
Gene: gli3 has been classified as Green List (High Evidence).
Victorian Clinical Genetics Services was added to GLI3. Panel: Limb disorders Phenotypes for gene GLI3 were set to Greig cephalopolysyndactyly syndrome 175700, Pallister-Hall syndrome 146510, Polydactyly, postaxial, types A1 and B 174200, Polydactyly, preaxial, type IV 174700, {Hypothalamic hamartomas, somatic} 241800, Polydactyly
Radboud University Medical Center, Nijmegen was added to GLI3. Panel: Limb disorders Illumina TruGenome Clinical Sequencing Services was added to GLI3. Panel: Limb disorders Expert list was added to GLI3. Panel: Limb disorders Emory Genetics Laboratory was added to GLI3. Panel: Limb disorders Expert Review Green was added to GLI3. Panel: Limb disorders UKGTN was added to GLI3. Panel: Limb disorders Model of inheritance for gene GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
London South East RGC GSTT was added to GLI3. Panel: Limb disorders
GLI3 was added to Limb disorders panel. Sources: Viapath
GLI3 was created by Ellen McDonagh