RESUMEN
Novel or rare damaging mutations have been implicated in the developmental pathogenesis of nonsyndromic cleft lip with or without cleft palate (nsCL ± P). Thus, we investigated the human genome for high-impact mutations that could explain the risk of nsCL ± P in our cohorts.We conducted next-generation sequencing (NGS) analysis of 130 nsCL ± P case-parent African trios to identify pathogenic variants that contribute to the risk of clefting. We replicated this analysis using whole-exome sequence data from a Brazilian nsCL ± P cohort. Computational analyses were then used to predict the mechanism by which these variants could result in increased risks for nsCL ± P.We discovered damaging mutations within the AFDN gene, a cell adhesion molecule (CAMs) that was previously shown to contribute to cleft palate in mice. These mutations include p.Met1164Ile, p.Thr453Asn, p.Pro1638Ala, p.Arg669Gln, p.Ala1717Val, and p.Arg1596His. We also discovered a novel splicing p.Leu1588Leu mutation in this protein. Computational analysis suggests that these amino acid changes affect the interactions with other cleft-associated genes including nectins (PVRL1, PVRL2, PVRL3, and PVRL4) CDH1, CTNNA1, and CTNND1.This is the first report on the contribution of AFDN to the risk for nsCL ± P in humans. AFDN encodes AFADIN, an important CAM that forms calcium-independent complexes with nectins 1 and 4 (encoded by the genes PVRL1 and PVRL4). This discovery shows the power of NGS analysis of multiethnic cleft samples in combination with a computational approach in the understanding of the pathogenesis of nsCL ± P.
RESUMEN
INTRODUCTION: This study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on the orthodontic patient. It also assessed the knowledge and attitude of patients to the COVID-19 infection and the willingness to carry out specific precautionary measures in the orthodontic clinics to mitigate the spread of the virus. METHODS: It was a cross-sectional descriptive study. Questionnaires were distributed to orthodontic patients via Google forms. The questionnaire assessed participants' knowledge, attitude, the impact of the COVID-19 pandemic on orthodontic treatment, and willingness to carry out infection control precautionary measures in the orthodontic clinic. RESULTS: A total of 304 responses were obtained; 83 males (27.3%), 221 females (72.7%) with a mean age of 35.6 years. Subjects demonstrated good knowledge of COVID-19 infection (94.7%). Most respondents (95%) considered the infection as dangerous and believed the orthodontic patient was at risk of contracting the disease but were willing regardless to carry on with their orthodontic treatment during the pandemic. Fear of contracting the COVID-19 virus during orthodontic appointments and missed orthodontic appointments (74%), and increased treatment time (50%) were the immediate and long-term concerns, respectively. A high acceptance rate of compliance to precautionary measures to mitigate virus spread in the clinic was observed. CONCLUSIONS: The COVID-19 pandemic has had a negative impact on the orthodontic treatment and the financial and emotional wellbeing of orthodontic patients. Patients were willing to continue with orthodontic management during the pandemic while complying with precautionary measures to prevent disease spread in the orthodontic practice setting.