Auriculo-condylar syndrome

Papagrigorakis, Manolis J.; Karamolegou, M; Vilos, G; Apostolidis, Charalabos; Karamesinis, Konstantinos; Synodinos, Philippos N.

doi:10.2319/052911-356.1

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…However, to date, only a limited number of sporadic ARCND cases have been reported. Ozturk et al [ 20 ], Papagrigorakis et al [ 21 ], Greig et al [ 10 ], and Yang et al [ 11 ] reported the use of a porous polyethylene prosthesis, DO, TMJ reconstruction, mandibular iliac bone transplantation, and Le Fort type I osteotomy to treat patients with ARCND. However, the application of preoperative orthodontics, DO, maxillary Le Fort I osteotomy, BSSRO, horizontal osteotomy, and genioplasty to treat adult patients with ARCND simultaneously has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report

Shi,

Rong,

Liu

et al. 2024

BMC Oral Health

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Background Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients’ lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. Case presentation Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient’s dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. Conclusions ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

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Section: Discussionmentioning

confidence: 99%

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report

Shi,

Rong,

Liu

et al. 2024

BMC Oral Health

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“…The dominant characteristic features of ACS include micrognathia, small mandibular condyle, and question-mark ear. Severe small mandible ACS patients usually need bilateral mandibular ramus enlargement, which could be obtained from distraction osteogenesis or orthognathic surgery, which is time-consuming and expensive [3]. On the contrary, excessive bone formation lays behind mandibular prognathism which is a maxillofacial disorder characterized by an abnormal forward projection of the lower jaw [4].…”

Section: Introductionmentioning

confidence: 99%

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis

Li¹,

Yuan²,

Ni³

et al. 2021

Int. J. Biol. Sci.

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Background: Congenital anomalies are increasingly becoming a global pediatric health concern, which requires immediate attention to its early diagnosis, preventive strategies, and efficient treatments. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (Gnai3) gene mutation has been demonstrated to cause congenital small jaw deformity, but the functions of Gnai3 in the disease-specific microRNA (miRNA) upregulations and their downstream signaling pathways during osteogenesis have not yet been reported. Our previous studies found that the expression of Mir24-2-5p was significantly downregulated in the serum of young people with overgrowing mandibular, and bioinformatics analysis suggested possible binding sites of Mir24-2-5p in the Gnai3 3'UTR region. Therefore, this study was designed to investigate the mechanism of Mir24-2-5p-mediated regulation of Gnai3 gene expression and explore the possibility of potential treatment strategies for bone defects. Methods: Synthetic miRNA mimics and inhibitors were transduced into osteoblast precursor cells to regulate Mir24-2-5p expression. Dual-luciferase reporter assay was utilized to identify the direct binding of Gnai3 and its regulator Mir24-2-5p. Gnai3 levels in osteoblast precursor cells were downregulated by shRNA (shGnai3). Agomir, Morpholino Oligo (MO), and mRNA were microinjected into zebrafish embryos to control mir24-2-5p and gnai3 expression. Relevant expression levels were determined by the qRT-PCR and Western blotting. CCK-8 assay, flow cytometry, and transwell migration assays were performed to assess cell proliferation, apoptosis, and migration. ALP, ARS and Von Kossa staining were performed to observe osteogenic differentiation. Alcian blue staining and calcein immersions were performed to evaluate the embryonic development and calcification of zebrafish. Results: The expression of Mir24-2-5p was reduced throughout the mineralization process of osteoblast precursor cells. miRNA inhibitors and mimics were transfected into osteoblast precursor cells. Cell proliferation, migration, osteogenic differentiation, and mineralization processes were measured, which showed a reverse correlation with the expression of Mir24-2-5p. Dual-luciferase reporter gene detection assay confirmed the direct interaction between Mir24-2-5p and Gnai3 mRNA. Moreover, in osteoblast precursor cells treated with Mir24-2-5p inhibitor, the expression of Gnai3 gene was increased, suggesting that Mir24-2-5p negatively targeted Gnai3. Silencing of Gnai3 inhibited osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization. Promoting effects of osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization by low expression of Mir24-2-5p was partially rescued upon silencing of Gnai3. In vivo, mir24-2-5p Agomir microinjection into zebrafish embryo resulted in shorter body length, smaller and retruded mandible, decreased cartilage development, and vertebral calcification, which was partially resc...

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“…There is wide clinical variability, including cases with isolated ear anomalies. Treatment is mainly corrective through surgical intervention for mandibular ramus lengthening using distraction osteogenesis and accompanied by orthodontic treatments and speech therapy 3. Understanding the aetiology of this disorder and elucidating genetic causes improve counselling and may lead to the development of preventive or therapeutic strategies, besides deepening our knowledge of craniofacial development.…”

Section: Introductionmentioning

confidence: 99%

New locus underlying auriculocondylar syndrome (ARCND): 430 kb duplication involvingTWIST1regulatory elements

et al. 2021

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BackgroundAuriculocondylar syndrome (ARCND) is a rare genetic disease that affects structures derived from the first and second pharyngeal arches, mainly resulting in micrognathia and auricular malformations. To date, pathogenic variants have been identified in three genes involved in the EDN1-DLX5/6 pathway (PLCB4, GNAI3 and EDN1) and some cases remain unsolved. Here we studied a large unsolved four-generation family.MethodsWe performed linkage analysis, resequencing and Capture-C to investigate the causative variant of this family. To test the pathogenicity of the CNV found, we modelled the disease in patient craniofacial progenitor cells, including induced pluripotent cell (iPSC)-derived neural crest and mesenchymal cells.ResultsThis study highlights a fourth locus causative of ARCND, represented by a tandem duplication of 430 kb in a candidate region on chromosome 7 defined by linkage analysis. This duplication segregates with the disease in the family (LOD score=2.88) and includes HDAC9, which is located over 200 kb telomeric to the top candidate gene TWIST1. Notably, Capture-C analysis revealed multiple cis interactions between the TWIST1 promoter and possible regulatory elements within the duplicated region. Modelling of the disease revealed an increased expression of HDAC9 and its neighbouring gene, TWIST1, in neural crest cells. We also identified decreased migration of iPSC-derived neural crest cells together with dysregulation of osteogenic differentiation in iPSC-affected mesenchymal stem cells.ConclusionOur findings support the hypothesis that the 430 kb duplication is causative of the ARCND phenotype in this family and that deregulation of TWIST1 expression during craniofacial development can contribute to the phenotype.

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Auriculo-condylar syndrome

Cited by 8 publications

References 17 publications

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis

New locus underlying auriculocondylar syndrome (ARCND): 430 kb duplication involvingTWIST1regulatory elements

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