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A novel GLI3 mutation affecting the zinc finger domain leads to preaxial-postaxial polydactyly-syndactyly complex.
BMC Med Genet. 2014 Sep 30; 15:110.BM

Abstract

BACKGROUND

Polydactyly is a highly common congenital limb defect. Extra digits may appear as an isolated anomaly or as a part of a syndrome. Mutations in GLI3 have been shown to cause Greig cephalopolysyndactyly, Pallister-Hall syndrome and non-syndromic polydactyly. Genotype-phenotype correlation studies of GLI3 mutations suggest a model by which mutations in the zinc-finger domain (ZFD) of GLI3 likely lead to syndromic polydactyly. Here we describe a rare case of autosomal dominant heterozygous missense mutation in the ZFD of GLI3 leading to a variable polydactyly-syndactyly complex.

CASE PRESENTATION

A large Jewish Moroccan family presented with apparently autosomal dominant heredity of bilateral thumb polydactyly in hands and feet combined with post-axial polydactyly type B or type A. Syndactyly was evident in most patients' hands and feet. Apart from head circumference beyond 90th percentile in some of the affected individuals, none had craniofacial dysmorphism. A novel GLI3 c.1802A > G (p.His601Arg) mutation was found in all affected individuals.

CONCLUSION

We demonstrate that a mutation in the ZFD domain of GLI3 leads to phenotypic variability, including an isolated limb phenotype. Thus, the variability in phenotypes caused by mutations in this master developmental regulator is more profound than has been previously suggested.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableThe Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva 84105, Israel. obirk@bgu.ac.il.

Pub Type(s)

Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25267529

Citation

Volodarsky, Michael, et al. "A Novel GLI3 Mutation Affecting the Zinc Finger Domain Leads to Preaxial-postaxial Polydactyly-syndactyly Complex." BMC Medical Genetics, vol. 15, 2014, p. 110.
Volodarsky M, Langer Y, Birk OS. A novel GLI3 mutation affecting the zinc finger domain leads to preaxial-postaxial polydactyly-syndactyly complex. BMC Med Genet. 2014;15:110.
Volodarsky, M., Langer, Y., & Birk, O. S. (2014). A novel GLI3 mutation affecting the zinc finger domain leads to preaxial-postaxial polydactyly-syndactyly complex. BMC Medical Genetics, 15, 110. https://doi.org/10.1186/s12881-014-0110-9
Volodarsky M, Langer Y, Birk OS. A Novel GLI3 Mutation Affecting the Zinc Finger Domain Leads to Preaxial-postaxial Polydactyly-syndactyly Complex. BMC Med Genet. 2014 Sep 30;15:110. PubMed PMID: 25267529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel GLI3 mutation affecting the zinc finger domain leads to preaxial-postaxial polydactyly-syndactyly complex. AU - Volodarsky,Michael, AU - Langer,Yshaia, AU - Birk,Ohad S, Y1 - 2014/09/30/ PY - 2014/04/13/received PY - 2014/09/24/accepted PY - 2014/10/1/entrez PY - 2014/10/1/pubmed PY - 2014/11/5/medline SP - 110 EP - 110 JF - BMC medical genetics JO - BMC Med Genet VL - 15 N2 - BACKGROUND: Polydactyly is a highly common congenital limb defect. Extra digits may appear as an isolated anomaly or as a part of a syndrome. Mutations in GLI3 have been shown to cause Greig cephalopolysyndactyly, Pallister-Hall syndrome and non-syndromic polydactyly. Genotype-phenotype correlation studies of GLI3 mutations suggest a model by which mutations in the zinc-finger domain (ZFD) of GLI3 likely lead to syndromic polydactyly. Here we describe a rare case of autosomal dominant heterozygous missense mutation in the ZFD of GLI3 leading to a variable polydactyly-syndactyly complex. CASE PRESENTATION: A large Jewish Moroccan family presented with apparently autosomal dominant heredity of bilateral thumb polydactyly in hands and feet combined with post-axial polydactyly type B or type A. Syndactyly was evident in most patients' hands and feet. Apart from head circumference beyond 90th percentile in some of the affected individuals, none had craniofacial dysmorphism. A novel GLI3 c.1802A > G (p.His601Arg) mutation was found in all affected individuals. CONCLUSION: We demonstrate that a mutation in the ZFD domain of GLI3 leads to phenotypic variability, including an isolated limb phenotype. Thus, the variability in phenotypes caused by mutations in this master developmental regulator is more profound than has been previously suggested. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/25267529/A_novel_GLI3_mutation_affecting_the_zinc_finger_domain_leads_to_preaxial_postaxial_polydactyly_syndactyly_complex_ L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-014-0110-9 DB - PRIME DP - Unbound Medicine ER -