Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies

Barbato, Ersilia; Traversa, Alice; Guarnieri, Rosanna; Giovannetti, Agnese; Genovesi, Maria Luce; Magliozzi, Maria Rosa; Paolacci, Stefano; Ciolfi, Andrea; Pizzi, Simone; Giorgio, Roberto Di; Tartaglia, Marco; Pizzuti, Antonio; Caputo, Viviana

doi:10.1016/j.archoralbio.2018.04.011

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…Although the allelic frequency in the healthy population of this variant was 2% according to the dbSNP database, some authors have suggested that it may make a significant contribution to NSTA but show a low penetrance [29]. In addition, it has been associated with a more severe phenotype in combination with other variants in a heterozygous state in a recent publication [46]. The phenotypes of our patients with p.Ser103Phe variant were consistent with both HED (4/5) and NSTA (1/5) (Table 4).…”

Section: Discussionmentioning

confidence: 99%

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population

Martínez-Romero

Ballesta-Martínez

López‐González

et al. 2019

Orphanet J Rare Dis

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BackgroundEctodermal dysplasias (ED) are a group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives. An attenuated phenotype is considered a non-syndromic trait when the patient is affected by only one impaired ectodermal structure, such as in non-syndromic tooth agenesis (NSTA) disorder. Hypohidrotic ectodermal dysplasia (HED) is the most highly represented ED. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common subtype, with an incidence of 1/50,000–100,000 males, and is associated with the EDA gene (Xq12-q13.1); the dominant and recessive subtypes involve the EDAR (2q13) and EDARADD (1q42.3) genes, respectively. The WNT10A gene (2q35) is associated more frequently with NSTA.Our goal was to determine the mutational spectrum in a cohort of 72 Spanish patients affected by one or more ectodermal derivative impairments referred to as HED (63/72) or NSTA (9 /72) to establish the prevalence of the allelic variants of the four most frequently associated genes. Sanger sequencing of the EDA, EDAR, EDARADD and WNT10A genes and multiplex ligation-dependent probe amplification (MLPA) were performed.ResultsA total of 61 children and 11 adults, comprising 50 males and 22 females, were included. The average ages were 5.4 and 40.2 years for children and adults, respectively. A molecular basis was identified in 51/72 patients, including 47/63 HED patients, for whom EDA was the most frequently involved gene, and 4/9 NSTA patients, most of whom had variants of WNT10A. Among all the patients, 37/51 had variants of EDA, 8/51 had variants of the WNT10A gene, 4/51 had variants of EDAR and 5/51 had variants of EDARADD. In 42/51 of cases, the variants were inherited according to an X-linked pattern (27/42), with the remaining showing an autosomal dominant (10/42) or autosomal recessive (5/42) pattern. Among the NSTA patients, 3/9 carried pathogenic variants of WNT10A and 1/9 carried EDA variants. A total of 60 variants were detected in 51 patients, 46 of which were different, and out of these 46 variants, 12 were novel.ConclusionsThis is the only molecular study conducted to date in the Spanish population affected by ED. The EDA, EDAR, EDARADD and WNT10A genes constitute the molecular basis in 70.8% of patients with a 74.6% yield in HED and 44.4% in NSTA. Twelve novel variants were identified. The WNT10A gene has been confirmed as the second molecular candidate that has been identified and accounts for one-half of non-EDA patients and one-third of NSTA patients. Further studies using next generation sequencing (NGS) will help to identify other contributory genes in the remaining uncharacterized Spanish patients.

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Section: Discussionmentioning

confidence: 99%

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population

Martínez-Romero

Ballesta-Martínez

López‐González

et al. 2019

Orphanet J Rare Dis

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“…However, this variant has been associated with NSTA, but with low penetrance and variable expressivity. (Bergendal et al, 2011;Arte et al, 2013;Barbato et al, 2018;Martínez-Romero et al, 2019). Although the heterozygous EDARADD c.413A > T mutation was detected in the patient and his unaffected brother, it was not in his affected sister or mother.…”

Section: Discussionmentioning

confidence: 75%

“…Interestingly, the digenic heterozygous variants of WNT10A and other genes in the EDA pathway, including EDA, EDAR, and EDARADD, have been found in several patients with NSTA (Arte et al, 2013;He et al, 2013;Barbato et al, 2018;Martínez-Romero et al, 2019). The WNT and EDA pathways are suggested to play complementary roles during tooth development (Yu et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Genotypic Features of Thai Patients With Nonsyndromic Tooth Agenesis and WNT10A Variants

et al. 2020

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Tooth agenesis is one of the most common orodental anomalies that demonstrate phenotypic and genotypic heterogeneity with a prevalence of 2.5%-7%. Mutations in WNT10A have been proposed to be the most common cause of nonsyndromic tooth agenesis (NSTA). The aim of this study was to characterize the dental features and genetic variants of NSTA in a Thai population. We recruited 13 unrelated patients with NSTA who attended the Faculty of Dentistry, Chulalongkorn University, Thailand, from 2017 to 2019. All 13 underwent whole exome sequencing that identified likely pathogenic genetic variants, all in WNT10A, in five patients. All five patients had second premolar agenesis, while three also had absent or peg-shaped upper lateral incisors. Patient 1 possessed a novel heterozygous duplication, c.916_918dupAAC (p.Asn306dup) in WNT10A. Patients 2 and 3 harbored a heterozygous and homozygous c.637G > A (p.Gly213Ser) in WNT10A, respectively. Patients 4 possessed a heterozygous c.511C > T (p.Arg171Cys) in WNT10A. Patient 5 harbored a homozygous c.511C > T (p.Arg171Cys) in WNT10A and a novel heterozygous c.413A > T (p.Asn138Ile) in EDARADD, suggesting digenic inheritance. We recruited another 18 family members of these five patients. Out of 23 participants, homozygous WNT10A variants were identified in 2 patients and heterozygous variants in 17 individuals. Both homozygous patients had NSTA. Eight out of 17 heterozygous individuals (8/17) had NSTA or a peg-shaped lateral incisor, indicating a 47% penetrance of the heterozygous variants or 53% (10/19) penetrance of either homozygous or heterozygous variants in WNT10A. The frequencies of the c.511C > T in our in-house 1,876 Thai exome database, Asian populations, and non-Asian populations were 0.016, 0.005-0.033, and 0.001, respectively; while those of the c.637G > A were 0.016, 0.004-0.029, and 0.000, respectively. In conclusion, our study reports two novel variants with one each in WNT10A and EDARADD, expanding the genotypic spectra of NSTA. Second premolar

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“…Information regarding the characteristics of the maxillary lateral incisors and their presence or absence was reported. Given the information according to the Becker classification, the elements have been divided according to the morphology into [ 16 ]: Absent; Conoids, when the mesio-distal width is greater than the cervical margin; Microdontics, when the mesio-distal width is equal to or less than its maxillary counterpart; Normal, when the mesio-distal width is greater than that of its maxillary counterpart, …”

Section: Methodsmentioning

confidence: 99%

“…However, this theory does not explain palatally impacted canines adjacent to normally developed incisors [ 9 ]. Canine anomalies are regarded as complex traits where the transmission of the trait is probably due to an autosomal dominant segregation model, with incomplete penetrance and variable expressivity [ 16 ]. In genetic theory, the palatal dislocation of the canine is frequently associated with other genetically determined dental anomalies, such as hypoplasia, dimension anomalies, and/or agenesis of the maxillary lateral incisors, aplasia of other teeth, and first molar infraocclusion [ 7 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Predictive Analysis of Maxillary Canine Impaction through Sella Turcica Bridging, Ponticulus Posticus Calcification, and Lateral Incisor Anomalies: A Retrospective Observational Study

Guarnieri

Germano

Altieri

et al. 2022

MPs

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Maxillary canine impaction is an increasing dental anomaly and is often related to other dento-skeletal anomalies. The aim of this work is to support the clinician in evaluating the relationship between a displaced maxillary canine and clinical (the features of lateral incisors)/skeletal (ponticulus posticus and sella turcica bridging) anomalies through orthopanoramic radiographs, lateral cephalograms, and plaster casts to identify the parameters that best predict maxillary canine impaction. A retrospective observational study was carried out on the analysis of the medical records, radiographic findings (panoramic radiographs and lateral cephalograms), and plaster casts of 203 orthodontic patients divided into a case group, with at least one impacted maxillary canine, and a control group, without an impaction. A chi-square test and logistic regression analysis were used to analyze the data. A statistically significant association was found between the impaction of the maxillary canine and the female sex, the bridging of the sella turcica, the ponticulus posticus calcification, and the anomaly of the lateral incisor; a logistic regression revealed that these significant variables were found to be positive predictors of impacted maxillary canines, particularly in reference to the impaction in the palatal area. Finding one of these clinical and radiographic elements can represent a predictive sign of the possible impaction of the maxillary canine.

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Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies

Cited by 7 publications

References 39 publications

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population

Phenotypic and Genotypic Features of Thai Patients With Nonsyndromic Tooth Agenesis and WNT10A Variants

Predictive Analysis of Maxillary Canine Impaction through Sella Turcica Bridging, Ponticulus Posticus Calcification, and Lateral Incisor Anomalies: A Retrospective Observational Study

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