TY - JOUR
T1 - A GLI3 variant leading to polydactyly in heterozygotes and Pallister-Hall-like syndrome in a homozygote
AU - Kariminejad, Ariana
AU - Ghaderi-Sohi, Siavash
AU - Keshavarz, Elham
AU - Hashemi, Seyed Abolghasem
AU - Parsimehr, Elham
AU - Szenker-Ravi, Emmanuelle
AU - Khatoo, Muznah
AU - Faraji Zonooz, Mehrshid
AU - Reversade, Bruno
AU - Najmabadi, Hossein
AU - Hennekam, Raoul C.
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
UR - https://onlinelibrary.wiley.com/doi/10.1111/cge.13730
UR - http://www.scopus.com/inward/record.url?scp=85081702600&partnerID=8YFLogxK
U2 - 10.1111/cge.13730
DO - 10.1111/cge.13730
M3 - Article
SN - 0009-9163
VL - 97
SP - 915
EP - 919
JO - Clinical Genetics
JF - Clinical Genetics
IS - 6
ER -