A novel p.Pro871Leu missense mutation in <i>SPECC1L</i> gene causing craniosynostosis in a patient

Bai, Shanshan; Geng, Yiyun; Duan, Huanan; Xu, Liang; Yu, Zheyuan; Yuan, Jie; Wei, Min

doi:10.1111/ocr.12473

Cited by 3 publications

(4 citation statements)

References 29 publications

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“…Interestingly, to date, ‘ SPECC1L syndrome’ cases have been associated with mutations within two domains of the protein, the second coiled coil domain (CCD2) and the calponin-homology domain (CHD) [ 26 , 27 , 34 , 35 , 38 , 39 ] ( Figure 1 ). On the contrary, missense variants residing outside, e.g., in coiled coil domains 3 (CCD3) or in other unstructured regions according to AlphaFold predictions, have been linked to non-syndromic orofacial clefting [ 37 ] and isolated craniosynostosis [ 36 ], raising the question of domain-dependent genotype–phenotype correlation. The variants we found in OS sporadic cases are located in CCD1 and CCD3 ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The missense variants identified in our work are shown below the scheme. The mutations reported so far in literature are shown above the scheme with the following color-code: blue—found in Teebi syndrome patients; yellow—found in OFC, CDH and craniosynostosis patients; red—found in ADOS; green—found in non-syndromic orofacial cleft cases [ 26 , 27 , 34 , 35 , 36 , 37 , 38 , 39 ].…”

Section: Figurementioning

confidence: 99%

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SPECC1L Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome

Migliore

Vendramin

McKee

et al. 2022

Genes

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Opitz G/BBB syndrome (OS) is a rare genetic developmental condition characterized by congenital defects along the midline of the body. The main clinical signs are represented by hypertelorism, laryngo–tracheo–esophageal defects and hypospadias. The X-linked form of the disease is associated with mutations in the MID1 gene located in Xp22 whereas mutations in the SPECC1L gene in 22q11 have been linked to few cases of the autosomal dominant form of this disorder, as well as to other genetic syndromes. In this study, we have undertaken a mutation screening of the SPECC1L gene in samples of sporadic OS cases in which mutations in the MID1 gene were excluded. The heterozygous missense variants identified are already reported in variant databases raising the issue of their pathogenetic meaning. Recently, it was reported that some clinical manifestations peculiar to OS signs are not observed in patients carrying mutations in the SPECC1L gene, leading to the proposal of the designation of ‘SPECC1L syndrome’ to refer to this disorder. Our study confirms that patients with diagnosis of OS, mainly characterized by the presence of hypospadias and laryngo–tracheo–esophageal defects, do not carry pathogenic SPECC1L mutations. In addition, SPECC1L syndrome-associated mutations are clustered in two specific domains of the protein, whereas the missense variants detected in our work lies elsewhere and the impact of these variants in the function of this protein is difficult to ascertain with the current knowledge and will require further investigations. Nonetheless, our study provides further insight into the SPECC1L syndrome classification.

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Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

SPECC1L Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome

Migliore

Vendramin

McKee

et al. 2022

Genes

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“…One of the genes contributing to this delamination defect in mice is Specc1l. Mutations in TWIST1 and SPECC1L lead to craniosynostosis and orofacial clefting in humans (Bai et al, 2021;Bhoj et al, 2019;Hall et al, 2020). Specc1l is a gene that encodes a novel coiled-coil domain containing protein, which stabilizes microtubules and actin of the cytoskeleton (Bhoj et al, 2019;Gfrerer et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

TWIST1 interacts with β/δ-catenins during neural tube development and regulates fate transition in cranial neural crest cells

et al. 2022

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Cell fate determination is a necessary and tightly regulated process for producing different cell types and structures during development. Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural plate borders into multiple cell lineages that differentiate into bone, cartilage, neurons, and glial cells. We previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation. Here, we investigated the mechanistic role of Twist1 and Irf6 at early stages of craniofacial development. Our data indicates that TWIST1 is expressed in endocytic vesicles at the apical surface and interacts with β/δ-CATENINS during neural tube closure, and Irf6 is involved in defining neural fold borders by restricting AP2α expression. Twist1 suppresses Irf6 and other epithelial genes in CNCCs during epithelial-to-mesenchymal transition (EMT) process and cell migration. Conversely, a loss of Twist1 leads to a sustained expression of epithelial and cell adhesion markers in migratory CNCCs. Disruption of TWIST1 phosphorylation in vivo leads to epidermal blebbing, edema, neural tube defects, and CNCC-derived structural abnormalities. Altogether, this study describes an uncharacterized function of mammalian Twist1 and Irf6 in the neural tube and CNCCs and provides new target genes of Twist1 involved in cytoskeletal remodeling. DNA variations within TWIST1 putative enhancers are significantly associated with human facial morphology in a large European cohort.

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“…Both Twist1 and Specc1l are involved in NC cell development and impact craniofacial structures in mice and humans. Mutations in TWIST1 and SPECC1L lead to craniosynostosis and orofacial clefting in humans (Bai et al, 2021;Bhoj et al, 2019;Hall et al, 2020). Specc1l is a gene that encodes a novel coiled-coil domain containing protein, which stabilizes microtubules and actin of the cytoskeleton (Bhoj et al, 2019;Gfrerer et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

TWIST1 interacts with adherens junction proteins during neural tube development and regulates fate transition in cranial neural crest cells

Bertól

Johnston

Ahmed

et al. 2021

Preprint

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Cell fate determination is a necessary and tightly regulated process for producing different cell types and structures during development. Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural fold borders into multiple cell lineages that differentiate into bone, cartilage, neurons, and glial cells. We previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation. Here, we investigated the mechanistic role of Twist1 and Irf6 at early stages of craniofacial development. Our data indicates that TWIST1 interacts with α/β/γ-CATENINS during neural tube closure, and Irf6 is involved in the structural integrity of the neural tube. Twist1 suppresses Irf6 and other epithelial genes in CNCCs during epithelial-to-mesenchymal transition (EMT) process and cell migration. Conversely, a loss of Twist1 leads to a sustained expression of epithelial and cell adhesion markers in migratory CNCCs. Disruption of TWIST1 phosphorylation in vivo leads to epidermal blebbing, edema, neural tube defects, and CNCC-derived structural abnormalities. Altogether, this study describes an uncharacterized function of Twist1 and Irf6 in the neural tube and CNCCs and provides new target genes of Twist1 involved in cytoskeletal remodeling. Furthermore, the association between DNA variations within TWIST1 putative enhancers and human facial morphology is also investigated.SUMMARY STATEMENTThis study uncovers a new function of Twist1 in neural tube development and epithelial-to-mesenchymal transition in cranial neural crest cells. Data further shows that Twist1-interacting Irf6 is involved in regulating neural tube integrity.

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A novel p.Pro871Leu missense mutation in SPECC1L gene causing craniosynostosis in a patient

Cited by 3 publications

References 29 publications

SPECC1L Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome

SPECC1L Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome

TWIST1 interacts with β/δ-catenins during neural tube development and regulates fate transition in cranial neural crest cells

TWIST1 interacts with adherens junction proteins during neural tube development and regulates fate transition in cranial neural crest cells

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