Rare single-nucleotide variants in oculo-auriculo-vertebral spectrum (OAVS)

Autor(es)

Zamariolli, Malu ^[1] ; Colovati, Mileny ^[1] ; Moyses-Oliveira, Mariana ^[1] ; Nunes, Natalia ^[1] ; dos Santos, Leonardo Caires ^[1] ; Alvarez Perez, Ana B. ^[1] ; Bragagnolo, Silvia ^[1] ; Melaragno, Maria Isabel ^[1]

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR GENETICS & GENOMIC MEDICINE; v. 7, n. 10 OCT 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 14/11572-8 - Rearranjos cromossômicos e sua importância na etiologia das doenças genéticas: investigação citogenômica e molecular
• Beneficiário: Maria Isabel de Souza Aranha Melaragno
• Modalidade de apoio: Auxílio à Pesquisa - Temático