Congenital limb abnormalities are the most common birth defects in new-borns. Polydactyly is one of the most common congenital limb malformations [
2]. Human embryos start to form at the end of the fourth week of embryonic development. After approximately 4 weeks, the interactions of the genes and various factors play decisive roles in the formation of normal morphology, function and finger number [
6]. During the formation of limbs, there are three interacting signalling centres that direct the formation of fingers. Abnormal genes in these signalling centres will result in congenital limb malformations. Recent studies have focused on genes and gene families related to limb development, such as
SHH,
ZRS and
GLI3 [
7]. Among them,
GLI3 is currently known to be an important signalling molecule that regulates the anteroposterior axis direction [the direction of the first finger (toe) to the fifth finger (toe)] in human embryo development [
8].
The
GLI3 gene is located in the 7p14.1 region of the chromosome and consists of 14 exons. The mRNA of
GLI3 is 8.5 kb in length and encodes a polypeptide chain consisting of 1580 amino acids [
9]. The protein can be divided into 3 parts that are associated with different genotype-phenotype correlations: the ZFD, the cyclic AMP-binding protein-binding domain (CBPD), and the transactivation domains 1 and 2 (TA1 and 2). The ZFD contains five highly conserved tandem zinc finger structures with specific DNA sequence affinity (2 cysteine and 2 histidine, C2H2). It is a central zinc finger transcription factor in the early development of vertebrate limbs [
10]. The mutation is near one of the C2H2s, which contains the 513–540 region in
GLI3. In some cases, mutations of the ZFD usually result in a reduced expression of
GLI3, which leads to an expanded expression of the active forms of
GLI3 (
GLI3A) compared to the repressor forms of
GLI3 (
GLI3R)
. These point mutations throughout the
GLI3 gene are well known for causing the GCPS phenotype. Instead, the boy we report carries a novel autosomal dominant heterozygous missense mutation NC_000007.14(NM_000168.5):c.1622C > T; p.(Thr541Met) near the ZFD of
GLI3 associated with isolated postaxial synpolydactyly. Some articles have suggested that the perturbation of the balance of GLI3R and GLI3A is connected to postaxial polydactyly. A mildly abnormal ratio of GLI3R to GLI3A can result in isolated postaxial polydactyly. Therefore, the mutation in our case may affect the normal function of the ZFD in a different manner. Further experiments will be necessary to confirm how this mutation works. We believe that there is practical significance for further studies of synpolydactyly.