Three novel genes tied to mandibular prognathism in eastern Mediterranean families.

INTRODUCTION: Mandibular prognathism (MP) is subject to major polygenic influence and segregates within families in autosomal dominance with variable expressivity and incomplete penetrance. We aimed to identify the inheritance pattern and genes and loci involved in the development of MP in Mediterranean families and to evaluate the dentoskeletal characteristics of affected individuals. METHODS: Fifty-one eastern Mediterranean families with individuals affected by MP were identified. Data and biospecimens were collected from 14 of the families, including clinical examination, lateral cephalography (on subjects with Class III malocclusion), and 5 mL blood drawn from consenting affected and nonaffected relatives. Next-generation sequencing (NGS) was performed on 8 families (7 Lebanese, 1 Lebanese/Syrian), including large numbers of affected individuals over many generations and severe conditions, with the use of whole-exome sequencing. RESULTS: Most pedigrees suggested autosomal-dominant inheritance with an equal number of affected male and female individuals. Affected individuals had macrognathic and prognathic mandibles with dentoalveolar compensation. Genetic screening did not correspond with previously reported MP-linked genes, but yielded 3 novel genes (C1orf167, NBPF8, NBPF9) on chromosome 1 potentially responsible for mandibular development and macrognathism. CONCLUSIONS: In this first genetic study with the use of NGS on the largest reported number of families with MP, novel genes (C1orf167, NBPF8, NBPF9) were associated with familial MP in the eastern Mediterranean population.

Serum microRNAs as potential biomarkers of mandibular prognathism.

OBJECTIVES: The aim of the study was to determine whether the expression levels of specific circulating serum microRNAs (miRNAs) are associated with mandibular prognathism (MP). METHODS: Sixty subjects in the early permanent dentition stage and 23 in the mixed dentition stage with MP were identified. Sixty-eight normal control subjects in the early permanent dentition stage and 24 in the mixed dentition stage were recruited for comparison. According to the microarray-based expression profiling, four serum miRNAs (let-7i-3p, miR-595, miR-16-2-3p, and miR-367-5p) were validated. RESULTS: In the MP groups, let-7i-3p was significantly over-expressed in subjects in the early permanent (P < 0.0005) and mixed (P < 0.001) dentitions, and miR-595 was significantly under-expressed (P < 0.004) in subjects in the early permanent (P < 0.004) and mixed (P < 0.0005) dentitions, compared with normal control groups. Multiple logistic regression analysis and receiver operating characteristic curve analysis revealed that let-7i-3p and miR-595 were able to significantly discriminate MP subjects from normal controls. CONCLUSION: Let-7i-3p and miR-595 could be potential, non-invasive biomarkers for the accurate early detection and diagnosis of MP, which may result in improved clinical management.

Anesthetic management of a patient with Bartter's syndrome undergoing orthognathic surgery.

Bartter's syndrome is a rare disorder characterized by severe hypokalemic alkalosis, marked elevation in plasma renin activity, pressor insensitivity to angiotensin II, and normal or low values of plasma sodium, plasma chloride, and blood pressure. Many of the clinical features and biochemical abnormalities appear to be secondary to chronic hypokalemia. We managed a 22-yr-old man requiring orthognathic surgery for correction of facial asymmetry under general anesthesia.