Homozygous GLI3 variants observed in three unrelated patients presenting with syndromic polydactyly.
GLI3
Greig cephalopolysyndactyly
OFD syndromes
Pallister-Hall
polydactyly
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
01
05
2021
received:
23
02
2021
accepted:
12
06
2021
pubmed:
24
7
2021
medline:
3
3
2022
entrez:
23
7
2021
Statut:
ppublish
Résumé
Polydactyly is a hallmark of GLI3 pathogenic variants, with Greig cephalopolysyndactyly syndrome and Pallister-Hall syndrome being the two main associated clinical presentations. Homozygous GLI3 variants are rare instances in the literature, and mendelian dominance is the accepted framework for GLI3-related diseases. Herein, we report three unrelated probands, presenting with polydactyly, and homozygous variants in the GLI3 gene. First, a 10-year-old girl, whose parents were first-degree cousins, presented with bilateral postaxial polydactyly of the hands, developmental delay and multiple malformations. Second, a male newborn, whose parents were first-degree cousins, presented with isolated bilateral postaxial polysyndactyly of the hands and the feet. Third, an adult male, whose parents were first-degree cousins, had bilateral mesoaxial polydactyly of the hands, with severe intellectual disability and multiple malformations. All three probands carried homozygous GLI3 variants. Strikingly, the parents also carried the child's variant, in the heterozygous state, without any clinical sign of GLI3 disease. Given the clinical presentation of our patients, the rarity and predicted high pathogenicity of the variants observed, and the absence of other pathogenic variants, we suggest that these GLI3 homozygous variants are causal. Moreover, the parents were heterozygous for the observed variants, but were clinically unremarkable, suggesting that these variants are hypomorphic alleles.
Identifiants
pubmed: 34296525
doi: 10.1002/ajmg.a.62426
doi:
Substances chimiques
GLI3 protein, human
0
Nerve Tissue Proteins
0
Zinc Finger Protein Gli3
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
3831-3837Informations de copyright
© 2021 Wiley Periodicals LLC.
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