RESUMO
A girl with a unilateral cleft lip, alveolus and palate, tooth agenesis, and mild dysmorphic features, without a specific underlying syndrome diagnosis, was genotypically characterized and phenotypically described. Cleft gene panel analysis, single-nucleotide polymorphism (SNP) array, whole genome sequencing (WGS), whole exome sequencing, and quantitative PCR (Q-PCR) analysis were used as diagnostic tests. SNP array revealed a maternal deletion at 16q24.1, encompassing the cleft candidate gene USP10. WES revealed an additional de novo Loss-of-Function variant (p.(Asn838fs)) in the Zinc-Finger-Homeobox-4 (ZFHX4) gene. Q-PCR was performed to explore the effect of the ZFHX4 variant and the deletion in 16q24.1. The mRNA expression of a selection of putative target genes involved in orofacial clefting showed a lowered expression of USP10 (52%), CRISPLD2 (31%), and CRISPLD1 (1%) compared to the control. IRF6 showed no difference in gene expression. This case supports ZFHX4 as a novel cleft gene and suggests USP10 may contribute to the etiology of orofacial clefts in humans.
Assuntos
Fenda Labial , Fissura Palatina , Feminino , Humanos , Fenda Labial/genética , Fissura Palatina/genética , Fatores Reguladores de Interferon/genética , Polimorfismo de Nucleotídeo Único , Ubiquitina Tiolesterase/genética , Fatores de Transcrição/genética , Proteínas de Homeodomínio/genéticaRESUMO
OBJECTIVES: To assess treatment outcome (transversal and sagittal dental arch relationships) and its determinants in complete bilateral cleft lip and palate (BCLP) evaluated with the modified Huddart-Bodenham scoring system and the BCLP Yardstick. MATERIALS AND METHODS: Multiple electronic databases were searched without time limitation. Randomized clinical trials, cohort and case control studies using BCLP Yardstick and/or modified Huddart-Bodenham system to judge treatment outcome of patients with BCLP were included. The Risk of Bias in Nonrandomized Studies of Interventions tool and Grading of Recommendations, Assessment, Development, and Evaluation was used. RESULTS: Of the 528 studies identified by the electronic search, only eight retrospective studies met the inclusion criteria and were included. A total of 12 cleft centers were represented. All treatment protocols differed and background information was underreported. The results for the BCLP yardstick showed that all except the centers in New Zealand had a mean score lower than 3, indicating good treatment results. However, these studies had a moderate to high risk of bias. The modified Huddart-Bodenham scores were negative in all studies. No further meta-analysis was done due to heterogeneity and high risk of bias. The quality of evidence was graded as very low. CONCLUSION: Results for the dental arch relationship of studies in complete BCLP and possible determinants were not synthesized due to very low quality of evidence. Clinical research for patients with BCLP should focus on sound methodological designs to enable evidence-based decision making to improve treatment for patients with BCLP and thereby hopefully their quality of life.