Objetivo: Hendiduras orofaciales (OFC) Son defectos de nacimiento comunes, incluido el labio hendido., labio y paladar hendido, y paladar hendido. Las OFC tienen etiologías heterogéneas, complicando el diagnóstico clínico porque no siempre es evidente si la causa es mendeliana, ambiental, o multifactorial. Actualmente no se realiza la secuenciación de OFC aisladas o esporádicas.; por lo tanto, estimamos el rendimiento diagnóstico para 418 genes en 841 casos y 294 controles.
Métodos: evaluamos 418 genes que utilizan secuenciación del genoma y variantes seleccionadas para evaluar su patogenicidad utilizando los criterios del American College of Medical Genetics.
Resultados: 9.04% de casos y 1.02% de controles tenían “probablemente patógeno” variantes (PAG < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance. Conclusion: These results underscore the etiological heterogeneity of OFCs and suggest sequencing could reduce the diagnostic gap in OFCs.
Bluesky