The Enigmatic Etiology of Oculo-Auriculo-Vertebral Spectrum (OAVS): An Exploratory Gene Variant Interaction Approach in Candidate Genes
Por:
Estandia-Ortega, Bernardette, Reyna-Fabián M.E., Velázquez-Aragón J.A., Gonzalez-del Angel, Ariadna, Fernandez-Hernandez, Liliana, Alcántara-Ortigoza M.A.
Publicada:
1 nov 2022
Resumen:
The clinical diagnosis of oculo-auriculo-vertebral spectrum (OAVS) is
established when microtia is present in association with hemifacial
hypoplasia (HH) and/or ocular, vertebral, and/or renal malformations.
Genetic and non-genetic factors have been associated with microtia/OAVS.
Although the etiology remains unknown in most patients, some cases may
have an autosomal dominant, autosomal recessive, or multifactorial
inheritance. Among the possible genetic factors, gene-gene interactions
may play important roles in the etiology of complex diseases, but the
literature lacks related reports in OAVS patients. Therefore, we
performed a gene-variant interaction analysis within five microtia/OAVS
candidate genes (HOXA2, TCOF1, SALL1, EYA1 and TBX1) in 49 unrelated
OAVS Mexican patients (25 familial and 24 sporadic cases). A
statistically significant intergenic interaction (p-value < 0.001) was
identified between variants p.(Pro1099Arg) TCOF1 (rs1136103) and
p.(Leu858=) SALL1 (rs1965024). This intergenic interaction may suggest
that the products of these genes could participate in pathways related
to craniofacial alterations, such as the retinoic acid (RA) pathway. The
absence of clearly pathogenic variants in any of the analyzed genes does
not support a monogenic etiology for microtia/OAVS involving these genes
in our patients. Our findings could suggest that in addition to
high-throughput genomic approaches, future gene-gene interaction
analyses could contribute to improving our understanding of the etiology
of microtia/OAVS.
Filiaciones:
Estandia-Ortega, Bernardette:
Molecular Biology Laboratory, Medical Research Sudirectorate, National Institute of Pediatrics, Mexico City, 04530, Mexico
Biology Sciences, Posgrade Unit, National Autonomous University of Mexico, Mexico City, 04510, Mexico
Reyna-Fabián M.E.:
Molecular Biology Laboratory, Medical Research Sudirectorate, National Institute of Pediatrics, Mexico City, 04530, Mexico
Velázquez-Aragón J.A.:
Experimental Oncology Laboratory, Experimental Medicine Subdirectorate, National Institute of Pediatrics, Mexico City, 04530, Mexico
Gonzalez-del Angel, Ariadna:
Molecular Biology Laboratory, Medical Research Sudirectorate, National Institute of Pediatrics, Mexico City, 04530, Mexico
Fernandez-Hernandez, Liliana:
Molecular Biology Laboratory, Medical Research Sudirectorate, National Institute of Pediatrics, Mexico City, 04530, Mexico
Alcántara-Ortigoza M.A.:
Molecular Biology Laboratory, Medical Research Sudirectorate, National Institute of Pediatrics, Mexico City, 04530, Mexico
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