Targeted exome sequencing reveals a novel <i>GLI3</i> mutation in a Chinese family with nonsyndromic polydactyly

Zhao, Xiang-Yu; Xu, Hongyan; Liu, Xiaxia; Lin, Li

doi:10.1002/dvdy.89

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…It has been demonstrated that GLI3 possesses a dual function, including a transcriptional activator of SHH signaling pathway by phosphorylated full‐length GLI3 and a repressor by C‐terminally truncated CLI3. Recently, several novel mutations of GLI3 have been identified in the patients with PD, including mutation c. 1622C > T (Zou et al, 2019), c.2148delA (Zhao, Xu, Liu, & Li, 2019), c.3437_3453delTCGAGCAGCCCTGCCCC, and c.3997C > T (Chen et al, 2019), c.1180C > TT (Ni et al, 2019). Therefore, our results suggested that this frameshift mutation of GLI3 might be a main reason for preaxial PD type IV phenotype in this Chinese family.…”

Section: Discussionmentioning

confidence: 99%

Novel frameshift mutations of ANKUB1, GLI3, and TAS2R3 associated with polysyndactyly in a Chinese family

Zhang

Chen

et al. 2020

Molec Gen & Gen Med

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Background Polysyndactyly (PSD) is an autosomal dominant genetic limb malformation caused by mutations. Methods Whole exome sequencing and Sanger sequencing were used to determine the mutations in PSD patients. Luciferase reporter assay was performed to determine the effect of GLI3 mutation on its transcriptional activity. Results In this study, we investigated the gene mutations of three affected individuals across three generations. The frameshift mutations of GLI3 (NM_000168:c.4659del, NP_000159.3: p.Ser1553del), ANKUB1 (NM_001144960:c.1385del, NP_001138432.1: p.Pro462del), and TAS2R3 (NM_016943:c.128_131del, NP_058639.1: p.Leu43del) were identified in the three affected individuals, but not in three unaffected members by whole exome sequencing and sanger sequencing. Luciferase reporter assay demonstrated that GLI3 mutation reduced the transcriptional activity of GLI3. The results from SMART analysis showed that the frameshift mutation of TAS2R3 altered most protein sequence, which probably destroyed protein function. Although the frameshift mutation of ANKUB1 did not locate in ankyrin repeat domain and ubiquitin domain, it might influence the interaction between ANKUB1 and other proteins, and further affected the ubiquitinylation. Conclusion These results indicated that the frameshift mutations of GLI3, ANKUB1, and TAS2R3 might alter the functions of these proteins, and accelerated PSD progression.

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Section: Discussionmentioning

confidence: 99%

Novel frameshift mutations of ANKUB1, GLI3, and TAS2R3 associated with polysyndactyly in a Chinese family

Zhang

Chen

et al. 2020

Molec Gen & Gen Med

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“…Shh signaling is mediated by three Gli genes in vertebrates (Gli1, Gli2, and Gli3). Of these, Gli3 is essential for limb development, as evidenced by the polydactylous phenotype of the extra-toes ( Xt ) Gli3 mutant allele [ 15 ]. Interestingly, it has been recently shown that Gli3 and HoxD12 interact both genetically and physically to modulate the function of Gli3R.…”

Section: Introductionmentioning

confidence: 99%

All-trans-retinoic acid suppresses rat embryo hindlimb bud mesenchymal chondrogenesis by modulating HoxD9 expression

Hong

Xie

et al. 2021

Bioengineered

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In vertebrates, 5 -Hoxd genes (Hoxd9), which are expressed in the hindlimb bud mesenchyme, participate in limb growth and patterning in early embryonic development. In the present study, We investigated the mechanisms by which ATRA regulates cultured E12.5 rat embryo hindlimb bud mesenchymal cells (rEHBMCs). Following exposure to ATRA over 24 h, mRNA and protein expression levels of HoxD9 were evaluated by reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), and western blotting. Flow cytometry was used to detect apoptosis. ATRA inhibited the condensation and proliferation, and promoted the apoptosis rate of the rEHBMCs in a dose-dependent manner. Sox9 and Col2a1 in rEHBMCs were downregulated by ATRA in a dose-dependent manner at both mRNA and protein levels. Similarly, HoxD9 was downregulated by ATRA in a dose-dependent manner, in parallel with the cartilagespecific molecules Sox9 and Col2a1. Both qPCR and western blotting showed that both Shh and Gli3 were downregulated. Overexpression of HoxD9 reversed the effects of ATRA. These results demonstrate that ATRA suppresses chondrogenesis in rEHBMCs by inhibiting the expression of HoxD9 and its downstream protein targets, including Sox9 and Col2a1. This effect may also be correlated with inhibition of the Shh-Gli3 signaling pathway.

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Targeted exome sequencing reveals a novel GLI3 mutation in a Chinese family with nonsyndromic polydactyly

Cited by 2 publications

References 17 publications

Novel frameshift mutations of ANKUB1, GLI3, and TAS2R3 associated with polysyndactyly in a Chinese family

Novel frameshift mutations of ANKUB1, GLI3, and TAS2R3 associated with polysyndactyly in a Chinese family

All-trans-retinoic acid suppresses rat embryo hindlimb bud mesenchymal chondrogenesis by modulating HoxD9 expression

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