A GLI3 variant leading to polydactyly in heterozygotes and Pallister-Hall-like syndrome in a homozygote.
Clin Genet
; 97(6): 915-919, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32112393
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anormalidades Múltiplas
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Dedos do Pé
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Polidactilia
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Síndrome de Pallister-Hall
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Dedos
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Proteína Gli3 com Dedos de Zinco
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Proteínas do Tecido Nervoso
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article