A novel GLI3 mutation affecting the zinc finger domain leads to preaxial-postaxial polydactyly-syndactyly complex

BMC Medical Genetics

Ohad S Birk¹  Yshaia Langer²  Michael Volodarsky³ 

[1] Genetics Institute, Soroka Medical Center, Beer-Sheva 84101, Israel;Department of Pediatrics, Shaare-Zedek Medical Center, Jerusalem, Israel;The 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

关键词: Zinc finger;    C2H2;    Mutation;    GLI3;    GCPS;    Syndactyly;    Polydactyly;   

Others  :  1090632
DOI  :  10.1186/s12881-014-0110-9

 received in 2014-04-13, accepted in 2014-09-24,  发布年份 2014

【 摘 要 】

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 90^th 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.

【 授权许可】

   
2014 Volodarsky et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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