Novel MYT1 variants expose the complexity of oculo-auriculo-vertebral spectrum genetic mechanisms

Author(s)

Zamariolli, Malu ^[1] ; Burssed, Bruna ^[1] ; Moyses-Oliveira, Mariana ^[1] ; Colovati, Mileny ^[1] ; Bellucco, Fernanda Teixeira da Silva ^[1] ; dos Santos, Leonardo Caires ^[1] ; Alvarez Perez, Ana Beatriz ^[1] ; Bragagnolo, Silvia ^[1] ; Melaragno, Maria Isabel ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Sao Paulo - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF MEDICAL GENETICS PART A; v. 185, n. 7 APR 2021.
• Web of Science Citations: 0

Abstract

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by anomalies mainly involving the structures derived from the first and second pharyngeal arches. The spectrum presents with heterogeneous clinical features and complex etiology with genetic factors not yet completely understood. To date, MYT1 is the most important gene unambiguously associated with the spectrum and with functional data confirmation. In this work, we aimed to identify new single nucleotide variants (SNVs) affecting MYT1 in a cohort of 73 Brazilian patients diagnosed with OAVS. In addition, we investigated copy number variations (CNVs) encompassing this gene or its cis-regulatory elements and compared the frequency of these events in patients versus a cohort of 455 Brazilian control individuals. A new SNV, predicted as likely deleterious, was identified in five unrelated patients with OAVS. All five patients presented hearing impairment and orbital asymmetry suggesting an association with the variant. CNVs near MYT1, located in its neighboring topologically associating domain (TAD), were found to be enriched in patients when compared to controls, indicating a possible involvement of this region with OAVS pathogenicity. Our findings highlight the genetic complexity of the spectrum that seems to involve more than one variant type and inheritance patterns. (AU)

• FAPESP's process: 14/11572-8 - Chromosomal rearrangements and their relevance in the etiology of genetic disorders: cytogenomic and molecular investigation
• Grantee: Maria Isabel de Souza Aranha Melaragno
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/23794-7 - Investigative approach in cleft lip and palate and congenital cadiopathy related to 22q11.2 deletion syndrome using open array and aGH techniques
• Grantee: Vera Lúcia Gil da Silva Lopes
• Support Opportunities: Regular Research Grants