Identification of genomic imbalances in oral clefts

Lustosa-Mendes, Elaine; Santos, Ana Paula dos; Vieira, Társis Paiva; Ribeiro, Erlane Marques; Rezende, Adriana Augusto de; Fett‐Conte, Agnes Cristina; Cavalcanti, Denise Pontes; Félix, Têmis Maria; Monlleó, Isabella Lopes; Gil-da-Silva-Lopes, Vera Lúcia

doi:10.1016/j.jped.2020.06.005

Cited by 6 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, Lustosa-Mendes and colleagues reported on the predictive value of the presence of additional minor anomalies in diagnostics of a large cleft cohort; the mean number of minor signs in their oral cleft cohort was statistically higher in cases with abnormal chromosomal microanalysis results [Lustosa-Mendes et al, 2021]. This phenomenon was also described for other disorders, e.g., autism [van Daalen et al, 2011].…”

Section: Discussionmentioning

confidence: 89%

Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands

Wurfbain,

Cox,

van Dooren

et al. 2023

Mol Syndromol

View full text Add to dashboard Cite

Objectives: Clefts of the lip, alveolus and/or palate (CLA/P) are the most common craniofacial congenital malformations in humans. These oral clefts can be divided into non-syndromic (isolated) and syndromic forms. Many cleft-related syndromes are clinically variable and genetically heterogeneous, making it challenging to distinguish syndromic from non-syndromic cases. Recognition of syndromic/genetic causes is important for personalized tailored care, identification of (unrecognized) comorbidities, and accurate genetic counseling. Therefore, next generation sequencing (NGS)-based targeted gene panel testing is increasingly implemented in diagnostics of CLA/P patients. In this retrospective study, we assess the yield of NGS gene panel testing in a cohort of CLA/P cases. Methods: Whole exome sequencing (WES) followed by variant detection and interpretation in an a priori selected set of genes associated with CLA/P phenotypes was performed in 212 unrelated CLA/P patients after genetic counseling between 2015 and 2020. Medical records including family history and results of additional genetic tests were evaluated. Results: In 24 CLA/P cases (11.3%), a pathogenic genetic variant was identified. Twenty out of these 24 had a genetic syndrome requiring specific monitoring and follow-up. Six of these 24 cases (25%) were presumed to be isolated CLA/P cases prior to testing, corresponding to 2.8% of the total cohort. In eight CLA/P cases (3.8%) without a diagnosis after NGS-based gene panel testing, a molecular diagnosis was established by additional genetic analyses (e.g., SNP array, single gene testing, trio WES). Conclusion: This study illustrates NGS-based gene panel testing is a powerful diagnostic tool in the diagnostic workup of CLA/P patients. Also, in apparently isolated cases and non-familial cases, a genetic diagnosis can be identified. Early diagnosis facilitates personalized care for patients and accurate genetic counseling of their families.

show abstract

Section: Discussionmentioning

confidence: 89%

Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands

Wurfbain,

Cox,

van Dooren

et al. 2023

Mol Syndromol

View full text Add to dashboard Cite

show abstract

“…Since chromosomal imbalances are seen in about 15-20% of patients with intellectual disability or multiple congenital defects [24] and are found in up to 44.4% of individuals with microphthalmia and/or anophthalmia [19], searching for genomic imbalances was the rst strategy chosen for diagnosis. However, despite previous studies have demonstrated the importance of CMA in the investigation of syndromic MAC spectrum [4] and SOCs [5], none of the patients in this OC-MAC cohort presented pathogenic genomic imbalances, hence why the study was pursued with WES analysis.…”

Section: Discussionmentioning

confidence: 94%

“…The utility of chromosomal microarray analysis (CMA) for diagnosis of SOCs and ocular developmental anomalies (ODA) including MAC has already been demonstrated, with a diagnostic yield for typical SOCs between 9% [5] and 25.3% [6] and 13% for ODA [7]. Whole exome sequencing (WES) on trios has shown that several genes are implicated in MAC, including some that are increasingly expressed in many types of retinal cells [8].…”

Section: Introductionmentioning

confidence: 99%

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

Gil-da-Silva-Lopes

Atique-Tacla

Copelli

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…The presence of prematurity, weight, length, and head circumference at birth were found to be significantly lower when genomic imbalances are detected, while the number of minor signs were significantly higher. These data may improve the professional ability to detect and refer patients with syndromic OFC to genetic assessment earlier and are important since timely diagnosis and treatment are crucial to achieve a better quality of life and offer genetic counseling (Lustosa‐Mendes et al, 2020).…”

Section: Section 2: Genetic Multicentric Studies In the Brazilian Popmentioning

confidence: 99%

Brazil's Craniofacial Project: Different approaches on orofacial clefts and 22q11.2 deletion syndrome

Gil-da-Silva-Lopes

Atique-Tacla

Vieira

et al. 2020

American J of Med Genetics Pt C

Self Cite

View full text Add to dashboard Cite

This article reports the present situation of Brazilian health care in genetics for Orofacial Cleft (OFC) and 22q11.2 Deletions Syndrome (22q11.2 DS) based on research conducted by Brazil's Craniofacial Project (BCFP). Established in 2003, BCFP is a voluntary and cooperative network aiming to investigate the health care of people with these diseases and other craniofacial anomalies. The initiatives and research results are presented in four sections: (a) a comprehensive report of the Brazilian public health system in craniofacial genetics; (b) multicentric studies developed on OFC and 22q11.2 DS; (c) education strategies focused on addressing these conditions for both population and health-care professionals; and (d) the nosology through

show abstract

Identification of genomic imbalances in oral clefts

Cited by 6 publications

References 27 publications

Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands

Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands

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

Brazil's Craniofacial Project: Different approaches on orofacial clefts and 22q11.2 deletion syndrome

Contact Info

Product

Resources

About