Genome-wide DNA methylation analysis of a cohort of 41 patients affected by Oculo-auriculo-vertebral spectrum (OAVS).
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PROVIDER: PRJNA638638 | ENA |
REPOSITORIES: ENA
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Project description:Oculo-auriculo-vertebral spectrum (OAVS; OMIM 164210) is a rare developmental 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 having been reported in a few OAVS patients, but the etiology of the disease remains largely unknown. A multifactorial origin of the OAVS has been proposed, including the involvement of environmental or epigenetic mechanisms. To identify the epigenetic mechanisms contributing to OAVS, we evaluated the DNA-methylation profile of 41 affected patients by using a BeadChip 450K genome-wide approach. The analysis was first carried out at a group level by comparing the OAVS group methylation profile to the control group (n=48) revealing a slight epigenetic variation in a number of genes implicated in biological processes involving basic chromatin dynamics such as DNA packaging, chromatin assembly, protein-DNA organization, and gene silencing in patients compared to controls . A subsequent analysis focused on searching for Stochastic Epigenetic Variations (SEV) in individual profiles identified an increased number of SEV in OAVS patients compared to controls. Although no recurrent deregulated enriched region was evidenced, isolated patients harboring suggestive epigenetic variations, including changes in imprinted domains, were identified. The recognition of a different DNA methylation pattern in OAVS patients and the identification of isolated patients with suggestive epigenetic variations provide consistent evidences for the contribution of epigenetic mechanisms to the etiology of this complex and heterogeneous disorder.
2021-02-04 | GSE152204 | GEO
Project description: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.
| S-EPMC7866060 | biostudies-literature
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.
| S-EPMC7965278 | biostudies-literature
Project description:A 2-month-old boy presented to us with bilateral microtia, left lower motor neuron facial palsy, micrognathia, hemivertebra, bifid rib, bifid thumb and absent/hypoplastic right-sided depressor anguli oris. He had bilateral external auditory canal atresia, although response to loud sound was present. Brain stem evoked response audiometry (BERA) was advised at 3 months of age. Karyotype was normal. We diagnosed him as a case of oculo-auriculo-vertebral spectrum. Child was discharged on request by the family with the plan for bone-anchored hearing aid after BERA and plan for pinna and ear canal reconstruction at a later age but child did not come for any follow-up visit. On telephonic enquiry, it was found that he is thriving well but has developmental delay including speech delay. We conclude that children presenting with external ear abnormalities should be screened for multiple congenital anomalies so that a multidisciplinary approach to management can be planned.
| S-EPMC7931756 | biostudies-literature
Project description:We report on three unrelated patients with the 22q11.2 microdeletion syndrome (del22q11) who have phenotypic anomalies compatible with oculo-auriculo-vertebral spectrum (OAVS). Hemifacial microsomia, unilateral microtia, hearing loss, congenital heart/aortic arch arteries defects, and feeding difficulties were present in all three patients. Additional anomalies occasionally diagnosed included coloboma of the upper eyelid, microphthalmia, cerebral malformation, palatal anomalies, neonatal hypocalcemia, developmental delay, and laryngomalacia. Several clinical features characteristic of OAVS have been described in patients with del22q11 from the literature, including ear anomalies, hearing loss, cervical vertebral malformations, conotruncal cardiac defects, renal malformations, feeding and respiratory difficulties. Atretic ear with facial asymmetry has been previously described in one patient. Thus, clinical expression of hemifacial microsomia and microtia resembling OAVS should now be included within the wide phenotypic expression of del22q11. The occurrence of this manifestation in del22q11 is currently low. Nevertheless, patients with hemifacial microsomia and microtia associated with clinical features typically associated with del22q11 should now have for specific cytogenetic testing.
| S-EPMC4138507 | biostudies-literature
Project description:BACKGROUND:Oculo-auriculo-vertebral spectrum (OAVS) is a craniofacial developmental disorder that affects structures derived from the first and second pharyngeal arches. The clinically heterogeneous phenotype involves mandibular, oral, and ear development anomalies. Etiology is complex and poorly understood. Genetic factors have been associated, evidenced by chromosomal abnormalities affecting different genomic regions and genes. However, known pathogenic single-nucleotide variants (SNVs) have only been identified in MYT1 in a restricted number of patients. Therefore, investigations of SNVs on candidate genes may reveal other pathogenic mechanisms. METHODS:In a cohort of 73 patients, coding and untranslated regions (UTR) of 10 candidate genes (CRKL, YPEL1, MAPK1, NKX3-2, HMX1, MYT1, OTX2, GSC, PUF60, HOXA2) were sequenced. Rare SNVs were selected and in silico predictions were performed to ascertain pathogenicity. Likely pathogenic variants were validated by Sanger sequencing and heritability was assessed when possible. RESULTS:Four likely pathogenic variants in heterozygous state were identified in different patients. Two SNVs were located in the 5'UTR of YPEL1; one in the 3'UTR of CRKL and one in the 3'UTR of OTX2. CONCLUSION:Our work described variants in candidate genes for OAVS and supported the genetic heterogeneity of the spectrum.
| S-EPMC6785430 | biostudies-literature
Project description:UnlabelledOculo-auriculo-vertebral spectrum (OAVS) is a rare condition characterized by the involvement of the first branchial arches.PurposeTo investigate the ear abnormalities of a sample of patients with OAVS.Materials and methodsThe sample consisted of 12 patients with OAVS seen at the Clinical Genetics Unit, UFCSPA/CHSCPA. The study included only patients who underwent mastoid computed tomography and with normal karyotype. We performed a review of its clinical features, giving emphasis to the ear findings.ResultsNine patients were male, the ages ranged from 1 day to 17 years. Ear abnormalities were observed in all patients and involved the external (n = 12), middle (n = 10) and inner ear (n = 3). Microtia was the most frequent finding (n = 12). The most common abnormalities of the middle ear were: opacification (n = 2), displacement (n = 2) and malformation of the ossicular chain. Agenesis of the internal auditory canal (n = 2) was the most frequent alteration of the inner ear.ConclusionsEar abnormalities are variable in patients with OAVS and often there is no correlation between findings in the external, middle and inner ear. The evaluation of these structures is important in the management of individuals with OAVS.
| S-EPMC9450788 | biostudies-literature
Project description:Abstract A Japanese boy, presented with epibulbar dermoid and ipsilateral preauricular appendages, had a pit on his cheek of the same side. An atrial septal defect and vertebral fusions were also identified. He was diagnosed with a mild type of oculo-auriculo-vertebral spectrum (OAVS). At the age of 18 months, his cheek was swollen with a slight fever. An infected cyst and cutaneous fistula enveloped by the risorius muscle were extracted. It was assumed to be a remnant of the fissure between the maxillary and mandibular prominences. This was the first case of cutaneous fistula confirmed histologically with OAVS, although there seem to be more cases. The possibility of the mechanism of smiling cheek dimple is also discussed.
| S-EPMC9129258 | biostudies-literature
Project description:Oculo-facio-cardio-dental syndrome (OFCD) is a rare genetic disorder characterized by teeth with extremely long roots (radiculomegaly), and craniofacial, eye and cardiac abnormalities. The mutation of the transcriptional co-repressor BCOR has been identified as being responsible for oculo-facio-cardio-dental (OFCD) syndrome. Mesenchymal stem cells (MSCs) is isolated from the root apical papilla of an OFCD patient. Gene expression profiling is performed and compared between mutant MSCs and wild type MSCs. Total RNA were extracted from normal MSCs (MSCWT) and mutant MSCs (MSCO).
2009-07-23 | E-GEOD-15214 | biostudies-arrayexpress
Project description:Oculo-facio-cardio-dental syndrome (OFCD) is a rare genetic disorder characterized by teeth with extremely long roots (radiculomegaly), and craniofacial, eye and cardiac abnormalities. The mutation of the transcriptional co-repressor BCOR has been identified as being responsible for oculo-facio-cardio-dental (OFCD) syndrome. Mesenchymal stem cells (MSCs) is isolated from the root apical papilla of an OFCD patient. Gene expression profiling is performed and compared between mutant MSCs and wild type MSCs.
2009-07-23 | GSE15214 | GEO