Holoprosencephaly and septo-optic dysplasia

Gene: GLI3

Green List (high evidence)

*Genotype-phenotype correlation (PMID:24736735):
- PHS: truncation in the middle third of GLI3
- GCPS: PTVs elsewhere and other type of mutations

*Genotype-phenotype correlation b/w different types of polydactyly were suggested in PMID: 32591344:
-Anterior: NMD predicted variants
-Posterior: truncating variants, missense variants

PTVs in the middle third of gene: Result in a constitutive repressor protein. Cause PHS.
Haploinsufficiency due to PTVs elsewhere, or missense, splicing. Result in loss of DNA-binding capacity or activation of NMD or formation of unstable/mislocalised protein. Cause GCPS.

Several reported families have shown variable expressivity of phenotype (PMID: 18000979).

Created: 26 Feb 2021, 1:34 a.m. | Last Modified: 26 Feb 2021, 1:34 a.m.

Panel Version: 0.6462

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Polydactyly, postaxial, types A1 and B, MIM#174200; Greig cephalopolysyndactyly syndrome MIM#175700; Polydactyly, preaxial, type IV MIM#174700; Pallister-Hall syndrome MIM#146510

Publications

• PMID: 32591344
• 18000979
• 24736735

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

HPE mentioned as a rare manifestation of Palmister-Hall in OMIM. However, in a series of 76 individuals, no HPE reported.

Created: 24 Aug 2020, 9:19 a.m. | Last Modified: 24 Aug 2020, 9:19 a.m.

Panel Version: 0.29

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pallister-Hall syndrome, MIM# 146510

Publications

• 24736735

Green List (high evidence)

Transcription factor that interacts with cilia (OMIM).

PMID: 24736735; Well reported to cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister–Hall syndrome (PHS) depending on location of the variant. This paper reviews genotype/phenotype correlation in 55 families.

Created: 18 May 2020, 2:31 a.m. | Last Modified: 18 May 2020, 2:31 a.m.

Panel Version: 0.152

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Greig cephalopolysyndactyly syndrome (MIM#175700); Pallister-Hall syndrome (MIM#146510)

Publications

• 24736735