Dataset Information

Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS).

ABSTRACT: Oculo-auriculo-vertebral-spectrum (OAVS; OMIM 164210) is a rare disorder originating from abnormal development of the first and second branchial arch. The clinical phenotype is extremely heterogeneous with ear anomalies, hemifacial microsomia, ocular defects, and vertebral malformations being the main features. MYT1, AMIGO2, and ZYG11B gene variants were reported in a few OAVS patients, but the etiology remains largely unknown. A multifactorial origin has been proposed, including the involvement of environmental and epigenetic mechanisms. To identify the epigenetic mechanisms contributing to OAVS, we evaluated the DNA-methylation profiles of 41 OAVS unrelated affected individuals by using a genome-wide microarray-based methylation approach. The analysis was first carried out comparing OAVS patients with controls at the group level. It revealed a moderate epigenetic variation in a large number of genes implicated in basic chromatin dynamics such as DNA packaging and protein-DNA organization. The alternative analysis in individual profiles based on the searching for Stochastic Epigenetic Variants (SEV) identified an increased number of SEVs in OAVS patients compared to controls. Although no recurrent deregulated enriched regions were found, isolated patients harboring suggestive epigenetic deregulations were identified. The recognition of a different DNA methylation pattern in the OAVS cohort and the identification of isolated patients with suggestive epigenetic variations provide consistent evidence for the contribution of epigenetic mechanisms to the etiology of this complex and heterogeneous disorder.

SUBMITTER: Guida V

PROVIDER: S-EPMC7866060 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS).

Guida Valentina V Calzari Luciano L Fadda Maria Teresa MT Piceci-Sparascio Francesca F Digilio Maria Cristina MC Bernardini Laura L Brancati Francesco F Mattina Teresa T Melis Daniela D Forzano Francesca F Briuglia Silvana S Mazza Tommaso T Bianca Sebastiano S Valente Enza Maria EM Salehi Leila Bagherjad LB Prontera Paolo P Pagnoni Mario M Tenconi Romano R Dallapiccola Bruno B Iannetti Giorgio G Corsaro Luigi L De Luca Alessandro A Gentilini Davide D

International journal of molecular sciences 20210126 3

Oculo-auriculo-vertebral-spectrum (OAVS; OMIM 164210) is a rare disorder originating from abnormal development of the first and second branchial arch. The clinical phenotype is extremely heterogeneous with ear anomalies, hemifacial microsomia, ocular defects, and vertebral malformations being the main features. MYT1, AMIGO2, and ZYG11B gene variants were reported in a few OAVS patients, but the etiology remains largely unknown. A multifactorial origin has been proposed, incl ...[more]

PMID: 33530447

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Project description:Background and purposeCranial nerve abnormalities might be observed in hemifacial microsomia and microtia (oculo-auriculo-vertebral spectrum), but the rate, features, and relationship with functional impairment or phenotype severity have not yet been defined. This study aimed at investigating absence/asymmetry, abnormal origin, morphology and course of cranial nerves, and presence/asymmetry of the foramen ovale and inferior alveolar nerve canal in a cohort of oculo-auriculo-vertebral spectrum patients.Materials and methodsTwenty-nine patients with oculo-auriculo-vertebral spectrum (mean age, 7 years; age range, 0.2-31 years; 12 females) underwent brain MR imaging, CT, and neurologic evaluation; 19 patients had a more severe phenotype (Goldenhar syndrome).ResultsCranial nerve abnormalities were detected only in patients with Goldenhar syndrome (17/19, bilaterally in 8) and were involved the second (4/19), third (1/18), fifth (11/19), sixth (8/16), seventh (11/18), and eighth (8/18) cranial nerves. Multiple cranial nerve abnormalities were common (11/17). Eleven patients showed bone foramina abnormalities. Trigeminal and facial nerve dysfunctions were common (44% and 58%, respectively), especially in patients with Goldenhar syndrome. Trigeminal abnormalities showed a good correlation with ipsilateral dysfunction (P = .018), which further increased when bone foramina abnormalities were included. The facial nerve showed a trend toward correlation with ipsilateral dysfunction (P = .081). Diplopia was found only in patients with Goldenhar syndrome and was associated with third and sixth cranial nerve abnormalities (P = .006).ConclusionsAmong patients with oculo-auriculo-vertebral spectrum, cranial nerve morphologic abnormalities are common, correlate with phenotype severity, and often entail a functional impairment. The spectrum of cranial nerve abnormalities appears wider than simple hypo-/aplasia and includes an anomalous cisternal course and partial/complete fusion of diverse cranial nerves.

Dataset Information

Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS).

Publications

Genome-Wide DNA Methylation Analysis of a Cohort of 41 Patients Affected by Oculo-Auriculo-Vertebral Spectrum (OAVS).

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