Limb disordersGene: GLI1
Comment on list classification: Changing rating from red to green. >3 cases of variants in GLI1 in families with polydactyly
Created: 7 Aug 2019, 3:09 p.m. | Last Modified: 7 Aug 2019, 3:09 p.m.
Panel Version: 1.49
Associated with Polydactyly, postaxial, type A8 (#618123) and Polydactyly, preaxial I (#174400) in OMIM.
Postaxial Polydactyly Type A8:
PMID: 28973407 - Palencia-Campos et al. 2017- 3 cases. They report data from 3 families, 2 Turkish (1 consangineous),1 Pakistani (consangineous) with developmental defects overlapping with Ellis–van Creveld syndrome, including postaxial polydactyly of the hands and/or feet . Homozygous truncating mutations (NM_005269.2: c.2340G > A; p.Trp780*, NM_005269.2: c.1930C > T; p.Gln644*, NM_005269.2: c.337C > T; p.Arg113*) were identified in patients in all 3 families.
Note, in the extended members of family 1, one individual is reported with polydactyly but is heterozygous for the p.Trp780* variant (patient 3) and one individual with polydactyly but no p.Trp780* variant is reported (patient 4). Homozygosity mapping suggests that these results were consistent with GLI1-W780X being responsible for the phenotype of patients 1–2 and a different genetic variation or disease mechanism for the phenotypes of patients 3 and 4.
Polydactyly, preaxial I:
PMID: 30620395 - Ullah et al. 2019 - 1 case. Pakistani family segregating autosomal recessive form of pre‐axial polydactyly. 2 individuals from two parts of the family were sequenced and a novel homozygous missense mutation identified c.1517T>A; p.Leu506Gln) in the GLI1. The variant segregated with the disease phenotype in the family. It was not found in their in‐house exome sequence data from 70 additional unrelated Pakistani individuals with normal limb phenotypes but was found in heterozygous state in the gnomAD browser, with an allele frequency of 0.0002109, but not in homozygous state.
Created: 7 Aug 2019, 2:50 p.m. | Last Modified: 7 Aug 2019, 3:07 p.m.
Panel Version: 1.48
Gene listed in Table 1 in PMID: 30945277 as associated with polydactyly.
Created: 7 Aug 2019, 1:12 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLI1 were set to 28973407; 28973407
Phenotypes for gene: GLI1 were changed from Polydactyly, postaxial, type A8, 618123); Polydactyly, preaxial I, 174400 to Polydactyly, postaxial, type A8, 618123; Polydactyly, preaxial I, 174400
Phenotypes for gene: GLI1 were changed from to Polydactyly, postaxial, type A8, 618123); Polydactyly, preaxial I, 174400
Gene: gli1 has been classified as Green List (High Evidence).
gene: GLI1 was added gene: GLI1 was added to Limb disorders. Sources: Literature Mode of inheritance for gene: GLI1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GLI1 were set to 28973407; 28973407 Review for gene: GLI1 was set to AMBER