A GLI3 variant leading to polydactyly in heterozygotes and Pallister-Hall-like syndrome in a homozygote

Ariana Kariminejad, Siavash Ghaderi-Sohi, Elham Keshavarz, Seyed Abolghasem Hashemi, Elham Parsimehr, Emmanuelle Szenker-Ravi, Muznah Khatoo, Mehrshid Faraji Zonooz, Bruno Reversade, Hossein Najmabadi, Raoul C. Hennekam

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Variants in transcriptional activator Gli Kruppel Family Member 3 (GLI3) have been reported to be associated with several phenotypes including Greig cephalopolysyndactyly syndrome (MIM #175700), Pallister-Hall syndrome (PHS) (MIM #146510), postaxial polydactyly types A1 (PAPA1) and B (PAPB) (MIM #174200), and preaxial polydactyly type 4 (MIM #174700). All these disorders follow an autosomal dominant pattern of inheritance. Hypothalamic hamartomas (MIM 241800) is associated with somatic variants in GLI3. We report a related couple with parents having PAPA1 and PAPB, who had a fetus with a phenotype most compatible with PHS. Molecular analyses demonstrated homozygosity for a pathogenic GLI3 variant (c.1927C > T; p. Arg643*) in the fetus and heterozygosity in the parents. The genetic analysis in this family demonstrates that heterozygosity and homozygosity for the same GLI3 variant can cause a different phenotype. Furthermore, the occurrence of Pallister-Hall-like syndrome in a homozygous patient should be taken into account in genetic counseling of families with PAPA1/PAPB.
Original languageEnglish (US)
Pages (from-to)915-919
Number of pages5
JournalClinical Genetics
Issue number6
StatePublished - Jun 1 2020
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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