A recurrent missense variant in EYA3 gene is associated with oculo-auriculo-vertebral spectrum

Tingaud‐Sequeira, Angèle; Salaria, M; Stapleton, Rachel; Claverol, Stéphane; Plaisant, Claudio; Bonneu, Marc; Lopez, Estelle; Arveiler, Benoı̂t; Lacombe, Didier; Rooryck, Caroline

doi:10.1007/s00439-021-02255-6

Cited by 18 publications

(22 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among 122 OAVS patients screened, the same variant was identified in an individual from an unrelated family. Segregation assessment in both families showed incomplete penetrance and variable expressivity 56. EYA proteins are able to complex with SIX proteins for a transactivation role.…”

Section: Aetiologiesmentioning

confidence: 96%

“…Several zebrafish models were obtained through transient knockdown of gene expression for homologue genes of OAVS. In this way, myt1a ,52 zyg11 ,55 eya3 56 and vwa1 58 knockdown zebrafish models are described in the literature (table 4). In these models, common specific craniofacial features are retrieved in craniofacial cartilage architecture.…”

Section: Oavs Animal Modelsmentioning

confidence: 99%

“…Craniofacial cartilages alteration following toxic exposure or gene knockdown in zebrafish embryos. Ventral views of 5 dpf zebrafish embryos following early embryonic exposure to MPA or fluoxetine and transient inactivation of two homologue genes associated to OAVS, eya3 and myt1a 52 56. Arrows indicate abnormal cartilage shape.…”

Section: Oavs Animal Modelsmentioning

confidence: 99%

See 2 more Smart Citations

Oculo-auriculo-vertebral spectrum: new genes and literature review on a complex disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

Oculo-auriculo-vertebral spectrum (OAVS) or Goldenhar syndrome is due to an abnormal development of first and second branchial arches derivatives during embryogenesis and is characterised by hemifacial microsomia associated with auricular, ocular and vertebral malformations. The clinical and genetic heterogeneity of this spectrum with incomplete penetrance and variable expressivity, render its molecular diagnosis difficult. Only a few recurrent CNVs and genes have been identified as causatives in this complex disorder so far. Prenatal environmental causal factors have also been hypothesised. However, most of the patients remain without aetiology. In this review, we aim at updating clinical diagnostic criteria and describing genetic and non-genetic aetiologies, animal models as well as novel diagnostic tools and surgical management, in order to help and improve clinical care and genetic counselling of these patients and their families.

show abstract

Section: Aetiologiesmentioning

confidence: 96%

Section: Oavs Animal Modelsmentioning

confidence: 99%

See 1 more Smart Citation

Oculo-auriculo-vertebral spectrum: new genes and literature review on a complex disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…A recurrent mutation in Eya3 (resulting in an Asn358Ser substitution) causing oculo-auriculo-vertebral spectrum has recently been reported [ 81 ]. This mutation appeared to increase the half-life of EYA3 but have no impact on tyrosine phosphatase activity.…”

Section: Developmental Disorders Associated With Eya Mutationsmentioning

confidence: 99%

The Eyes Absent proteins in development and in developmental disorders

Soni

Roychoudhury

Hegde

2021

Biochemical Society Transactions

View full text Add to dashboard Cite

The Eyes Absent (EYA) transactivator-phosphatase proteins are important contributors to cell-fate determination processes and to the development of multiple organs. The transcriptional regulatory activity as well as the protein tyrosine phosphatase activities of the EYA proteins can independently contribute to proliferation, differentiation, morphogenesis and tissue homeostasis in different contexts. Aberrant EYA levels or activity are associated with numerous syndromic and non-syndromic developmental disorders, as well as cancers. Commensurate with the multiplicity of biochemical activities carried out by the EYA proteins, they impact upon a range of cellular signaling pathways. Here, we provide a broad overview of the roles played by EYA proteins in development, and highlight the molecular signaling pathways known to be linked with EYA-associated organ development and developmental disorders.

show abstract

“…The etiology of OAVS is still largely unknown and felt to be multifactorial due to both environmental (maternal diabetes, antenatal exposure to vasoactive medications, smoking and twinning) and genetic factors during early embryogenesis [4]. With the widespread adoption of exome or genome sequencing, several genes have now been associated with OAVS [6][7][8][9][10][11], although many have only been identified through segregation in multi-generational single families. Most recently, a large exome/ genome sequencing effort of trios identified haploinsufficient variants in SF3B2 in multiple families segregating OAVS [12].…”

Section: Introductionmentioning

confidence: 99%

Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome

et al. 2022

View full text Add to dashboard Cite

Oculo-auriculo-vertebral syndrome (OAVS) is a clinically heterogeneous disorder, with both genetic and environmental contributors. Multiple genes have been associated with OAVS and common molecular pathways, such as retinoic acid and the PAX-SIX-EYA-DACH (PSED) network, are being implicated in the disease pathophysiology. Biallelic homozygous nonsense or hypomorphic missense mutations in PAX1 cause otofaciocervical syndrome type 2 (OTFCS2), a similar but more severe multi-system disorder that can be accompanied by severe combined immunodeficiency due to thymic aplasia. Here we have identified a multi-generational family with mild features of OAVS segregating a heterozygous frameshift in PAX1. The four base duplication is expected to result in nonsense-mediated decay, and therefore cause a null allele. While there was full penetrance of the variant, expressivity of facial and ear features were variable. Our findings indicate there can be monoallelic and biallelic disorders associated with PAX1, and further implicate the PSED network in OAVS.

show abstract

A recurrent missense variant in EYA3 gene is associated with oculo-auriculo-vertebral spectrum

Cited by 18 publications

References 43 publications

Oculo-auriculo-vertebral spectrum: new genes and literature review on a complex disease

Oculo-auriculo-vertebral spectrum: new genes and literature review on a complex disease

The Eyes Absent proteins in development and in developmental disorders

Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome

Contact Info

Product

Resources

About