Identification of novel susceptibility genes for non-syndromic cleft lip with or without cleft palate using NGS-based multigene panel testing

Dąbrowska, Justyna; Biedziak, Barbara; Szponar‐Żurowska, Anna; Budner, Margareta; Jagodzińśki, Paweł P.; Płoski, Rafał; Mostowska, Adrianna

doi:10.1007/s00438-022-01919-w

Cited by 7 publications

(5 citation statements)

References 60 publications

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“…The patient inherited this novel p.Arg339Gly missense substitution from her father with cleft palate only (results not shown). This result may support the hypothesis of a common genetic link between the congenital lack of teeth and orofacial clefts, which are frequently co-occurring craniofacial defects [ 19 , 57 , 58 , 59 ]. In addition, it may confirm the assumption that dental anomalies are subclinical phenotypes of the OFC spectrum.…”

Section: Discussionsupporting

confidence: 80%

“…The IRF6 gene is one of the the key susceptibility genes susceptibility genes for OFC, of which common and rare alleles have been found etiologic in both non-syndromic and syndromic forms of this structural anomaly [ 62 , 63 ]. The IRF6 deleterious variants have also been detected in patients with CLP associated with TA [ 19 , 64 ]. Moreover, common variants of this gene are associated with an increased risk of ns-TA [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…The multi-gene panel was developed previously to identify rare variants underlying craniofacial anomalies, including non-syndromic cleft lip with or without cleft palate (ns-CL/P). The detailed methodology for panel design, library preparation, NGS sequencing and data analysis has been described previously [ 19 ]. Briefly, the panel was created to target the coding sequence of genes associated with non-syndromic and syndromic forms of orofacial clefts (OFC) and TA and genes encoding proteins implicated in signalling pathways critical for craniofacial and orodental development.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Novel Candidate Genes for Non-Syndromic Tooth Agenesis Identified Using Targeted Next-Generation Sequencing

Biedziak

Firlej

Dąbrowska

et al. 2022

JCM

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Non-syndromic tooth agenesis (ns-TA) is one of the most common dental anomalies characterized by the congenital absence of at least one permanent tooth (excluding third molars). Regarding the essential role of genetic factors in ns-TA aetiology, the present study aimed to identify novel pathogenic variants underlying hypodontia and oligodontia. In a group of 65 ns-TA patients and 127 healthy individuals from the genetically homogenous Polish population, the coding sequences of 423 candidate genes were screened using targeted next-generation sequencing. Pathogenic and likely pathogenic variants were identified in 37 (56.92%) patients, including eight nucleotide alternations of genes not previously implicated in ns-TA (CHD7, CREBBP, EVC, LEF1, ROR2, TBX22 and TP63). However, since only single variants were detected, future research is required to confirm and fully understand their role in the aetiology of ns-TA. Additionally, our results support the importance of already known ns-TA candidate genes (AXIN2, EDA, EDAR, IRF6, LAMA3, LRP6, MSX1, PAX9 and WNT10A) and provide additional evidence that ns-TA might be an oligogenic condition involving the cumulative effect of rare variants in two or more distinct genes.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Novel Candidate Genes for Non-Syndromic Tooth Agenesis Identified Using Targeted Next-Generation Sequencing

Biedziak

Firlej

Dąbrowska

et al. 2022

JCM

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“…Numerous types of congenital malformation can be screened at an early stage; for example, cleft lip and palate can be screened by genetic techniques or ultrasound inspection in the embryonic development period ( 52 , 53 ). Considering that DI is not a lethal or severely teratogenic congenital malformation and is hard to screen during its development, clinical therapy is more important than early detection or prevention.…”

Section: Discussionmentioning

confidence: 99%

Treatment opinions for dens invaginatus: A case series

Wei,

Wang,

Shen

et al. 2024

Exp Ther Med

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Dens invaginatus (DI) is a rare congenital dental malformation characterized by enamel or cementum folded into dentine. Such teeth are susceptible to caries, pulp infection or necrosis and periradicular lesion. The complex anatomy of this disease results in difficult treatment and a high rate of therapeutic failure. Therapeutic options, such as debriding and filling invagination, root canal treatment (RCT) and intentional replantation, vary according to the morphology and infection of the involved tooth. The present study reports five cases of DI with chronic apical periodontitis. The treatment strategies and procedures, including RCT, removing the invagination, intentional replantation and surgical treatment, are discussed according to the classification and the condition of pulp and periapical tissue. The study also reports the prognosis: All patients were followed up for ≥12 months and all teeth demonstrated periapical healing and clinical asymptomatic. In summary, appropriate treatment is based on accurate analysis of the anatomical variation in different types of DI and intentional replantation is a reliable and viable treatment to preserve the tooth.

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“…VUSes in other genes associated with oral clefts are present in patients 11 (SOX1) and 12 (FLNB and ARHGAP29) [33]. Other VUSes, which possibly have an additive effect in a polygenic mode of inheritance, will be discussed next (patients 10, 11 and 12).…”

Section: Genotype-phenotypementioning

confidence: 98%

Molecular investigation in Orofacial Clefts with Microphthalmia-Anophthalmia-Coloboma spectrum

Gil-da-Silva-Lopes

Atique-Tacla

Copelli

et al. 2023

Preprint

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Orofacial clefts (OC) are the most common birth defects in humans and approximately 30% of them form the group of syndromic orofacial clefts (SOCs). Microphthalmia/anophthalmia/coloboma spectrum (MAC) can be associated with OC, however the genetic etiologies of OC-MAC have been poorly characterized. This study describes genomic findings among individuals with OC-MAC recorded in the Brazilian Database on Craniofacial Anomalies (BDCA). Chromosomal microarray analysis (CMA) and Whole exome sequencing (WES) were performed in 17 individuals with OC-MAC. Genotype-phenotype correlation was based on clinical data available at the BDCA and on re-examination. No copy number variants (CNVs) classified as likely pathogenic or pathogenic were detected by CMA. WES allowed a conclusive diagnosis in six individuals (35.29%), two of them involving the CHD7 gene. Variant of uncertain significance (VUS) possibly associated to the phenotypes were found in six other individuals. Among the individuals with VUSes, three individuals presented variants in genes associated to defects of cilia structure and/or function. Investigation by WES seems to be the most effective method for diagnosis in OC-MAC. This study also reinforces the genetic heterogeneity of OC-MAC, highlights the presence of the CHD7 gene, and the importance of genes related to ciliopathies in this phenotype.

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Identification of novel susceptibility genes for non-syndromic cleft lip with or without cleft palate using NGS-based multigene panel testing

Cited by 7 publications

References 60 publications

Novel Candidate Genes for Non-Syndromic Tooth Agenesis Identified Using Targeted Next-Generation Sequencing

Novel Candidate Genes for Non-Syndromic Tooth Agenesis Identified Using Targeted Next-Generation Sequencing

Treatment opinions for dens invaginatus: A case series

Molecular investigation in Orofacial Clefts with Microphthalmia-Anophthalmia-Coloboma spectrum

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