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A GLI3 variant leading to polydactyly in heterozygotes and Pallister-Hall-like syndrome in a homozygote.
Clin Genet. 2020 06; 97(6):915-919.CG

Abstract

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.

Authors+Show Affiliations

Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.Department of Radiology, Mahdieh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Parsian Hospital, Tehran, Iran.Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.Institute of Medical Biology, Agency for Science, Technology, and Research, Singapore, Singapore.Institute of Medical Biology, Agency for Science, Technology, and Research, Singapore, Singapore.Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.Institute of Medical Biology, Agency for Science, Technology, and Research, Singapore, Singapore.Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.Department of Pediatrics, Amsterdam UMC, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32112393

Citation

Kariminejad, Ariana, et al. "A GLI3 Variant Leading to Polydactyly in Heterozygotes and Pallister-Hall-like Syndrome in a Homozygote." Clinical Genetics, vol. 97, no. 6, 2020, pp. 915-919.
Kariminejad A, Ghaderi-Sohi S, Keshavarz E, et al. A GLI3 variant leading to polydactyly in heterozygotes and Pallister-Hall-like syndrome in a homozygote. Clin Genet. 2020;97(6):915-919.
Kariminejad, A., Ghaderi-Sohi, S., Keshavarz, E., Hashemi, S. A., Parsimehr, E., Szenker-Ravi, E., Khatoo, M., Faraji Zonooz, M., Reversade, B., Najmabadi, H., & Hennekam, R. C. (2020). A GLI3 variant leading to polydactyly in heterozygotes and Pallister-Hall-like syndrome in a homozygote. Clinical Genetics, 97(6), 915-919. https://doi.org/10.1111/cge.13730
Kariminejad A, et al. A GLI3 Variant Leading to Polydactyly in Heterozygotes and Pallister-Hall-like Syndrome in a Homozygote. Clin Genet. 2020;97(6):915-919. PubMed PMID: 32112393.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2020/03/10/ PY - 2020/01/21/received PY - 2020/02/18/revised PY - 2020/02/24/accepted PY - 2020/3/1/pubmed PY - 2021/6/5/medline PY - 2020/3/1/entrez KW - GLI3 KW - Pallister-Hall syndrome KW - heterozygote KW - homozygote KW - postaxial polydactyly SP - 915 EP - 919 JF - Clinical genetics JO - Clin Genet VL - 97 IS - 6 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. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/32112393/A_GLI3_variant_leading_to_polydactyly_in_heterozygotes_and_Pallister_Hall_like_syndrome_in_a_homozygote_ L2 - https://doi.org/10.1111/cge.13730 DB - PRIME DP - Unbound Medicine ER -