Novel GLI3 Mutations in Chinese Patients with Non-syndromic Post-axial Polydactyly.

X Chen, L Yuan, H Xu, P Hu, Y Yang, Y Guo, Z Guo, H Deng

Journal: Current molecular medicine 2020;19(3):228-235

PMID: 30848202

Abstract

BACKGROUND

Polydactyly, characterized by supernumerary digits in the upper or lower extremities, is the most common congenital digital abnormalities. It derives from the defective patterning of anteroposterior axis of the developing limb, with various etiology and clinical heterogeneity. The patients with post-axial polydactyly type A (PAPA) have the typical symptom of a well-formed supernumerary digit outside the fifth digit.

OBJECTIVE

The aim of present study was to identify the causative mutations of two unrelated Han Chinese patients with non-syndromic PAPA.

METHODS

Two unrelated Han Chinese patients and 100 ethnicity-matched, unrelated normal controls were recruited for this study. BGISEQ-500 exome sequencing was performed in the two patients, followed by validation in the patients and 100 controls by using Sanger sequencing.

RESULTS

Two mutations in the GLI family zinc finger 3 gene (GLI3), including a frameshift mutation c.3437_3453delTCGAGCAGCCCTGCCCC (p.L1146RfsX95) and a nonsense mutation c.3997C>T (p.Q1333X), were identified in two patients but were absent in the 100 healthy controls.

CONCLUSION

The two GLI3 mutations, p.L1146RfsX95 and p.Q1333X, may account for non-syndromic PAPA in the two patients, respectively. The findings of this study may expand the mutational spectrum of GLI3-PAPA and provide novel insights into the genetic basis of polydactyly.

Address: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.; Department of Radiology, the Third Xiangya Hospital, Central South University, Changsha, China.; Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.; Department of Medical Information, Information Security and Big Data Research Institute, Central South University, Changsha, China.

DOI: 10.2174/1566524019666190308110122

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MeSH Terms: Adult, Chromosome Mapping, DNA Mutational Analysis, Female, Fingers, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Male, Mutation, Nerve Tissue Proteins, Phenotype, Polydactyly, Toes, Exome Sequencing, Young Adult, Zinc Finger Protein Gli3