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BACKGROUND: Taurodontism is a dental anomaly characterized by altered crown root ratio that is often diagnosed by radiographic evaluation. A three-dimensional cone beam computed tomography (CBCT) can aid in the diagnosis and treatment of taurodontic teeth. Only one study has reported the prevalence of taurodontism in a Saudi population. OBJECTIVE: Determine prevalence and other characteristics of taurodontism in permanent maxillary and mandibular molars, by CBCT in a dental center in Saudi Arabia. DESIGN: Cross-sectional. SETTING: College of dentistry. SUBJECTS AND METHODS: The first and second molars, maxillary and mandibular, from study participants of Saudi origin from Jazan region of Saudi Arabia were evaluated for taurodontism based on the criteria of Shifman and Chanannel. The degree of taurodontism was determined by the taurodontism index. Results were tabulated for analysis and the chi-square test was applied for the differences between age groups, genders, and maxillary and mandibular teeth. MAIN OUTCOME MEASURES: Characteristics of taurodontism. SAMPLE SIZE: 1839 teeth in 300 individuals. RESULTS: Taurodontism was seen in 24 (8%) of the study participants and in 71 teeth (3.9%). Taurodontism was significantly more prevalent in individuals between 21 and 40 years of age. Hypotaurodontism (67.6%, n=48) was most prevalent, followed by mesotaurodontism (23.9%, n=17) and hypertaurodontism (8.5%, n=6). The maxillary molars were more commonly involved than mandibular, but the results were not statistically significant. No significant differences in gender were observed. CONCLUSIONS: Dental clinicians should be familiar with the condition due to the clinical implications in oral surgery, endodontics and prosthodontics. The possibilities of a complex root canal system, an additional canal, difficulties in canal negotiation, instrumentation and subsequent obturation can be challenging for the clinician. LIMITATIONS: Conducted in a single dental center hence future studies with larger sample sizes in different regions of Saudi Arabia should be conducted to more accurately measure the prevalence. CONFLICTS OF INTEREST: None.

Summary We have previously described a heart-, eye-, and brain-malformation syndrome caused by homozygous loss-of-function variants in SMG9, which encodes a critical component of the nonsense-mediated decay (NMD) machinery. Here, we describe four consanguineous families with four different likely deleterious homozygous variants in SMG8, encoding a binding partner of SMG9. The observed phenotype greatly resembles that linked to SMG9 and comprises severe global developmental delay, microcephaly, facial dysmorphism, and variable congenital heart and eye malformations. RNA-seq analysis revealed a general increase in mRNA expression levels with significant overrepresentation of core NMD substrates. We also identified increased phosphorylation of UPF1, a key SMG1-dependent step in NMD, which most likely represents the loss of SMG8--mediated inhibition of SMG1 kinase activity. Our data show that SMG8 and SMG9 deficiency results in overlapping developmental disorders that most likely converge mechanistically on impaired NMD.

Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly. Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes. In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet–Biedl syndrome. In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.

Acute bronchitis is one of the commonest medical problems managed by health services, and one of the important clinical questions is how to diagnose it in primary care, and differentiate from other disease and careful step of management to resolve disease. In this review we discuss management strategies by family doctor. Electronic databases (PubMed/ Embase) were searched up to NOVEMBER, 2018, for relevant literature in the management of Acute bronchitis in primary care by family doctors. Acute bronchitis is a widespread disease identified by fever and coughing that is usually wheezy in nature which may or may not be productive. The condition occurs when the bronchi end up being inflamed because of either viral or microbial infection. Signs normally last for 2 weeks, however the connected cough can last for as much as 8 weeks. Acute bronchitis needs to be separated from acute inflammation of the tiny airways- asthma or bronchiolitis- which normally provides as modern coughing accompanied by wheezing, tachypnea, respiratory distress, and hypoxemia. It ought to also be distinguished from bronchiectasis, a unique phenomenon associated with irreversible dilatation of bronchi and chronic cough. The diagnosis of acute bronchitis is developed in a patient that has the unexpected beginning of coughing, with or without sputum expectoration, and without evidence of pneumonia, the common cold, acute asthma, or an acute exacerbation of chronic bronchitis.

We report the results of clinical exome sequencing (CES) on >2,200 previously unpublished Saudi families as a first-tier test. The predominance of autosomal-recessive causes allowed us to make several key observations. We highlight 155 genes that we propose to be recessive, disease-related candidates. We report additional mutational events in 64 previously reported candidates (40 recessive), and these events support their candidacy. We report recessive forms of genes that were previously associated only with dominant disorders and that have phenotypes ranging from consistent with to conspicuously distinct from the known dominant phenotypes. We also report homozygous loss-of-function events that can inform the genetics of complex diseases. We were also able to deduce the likely causal variant in most couples who presented after the loss of one or more children, but we lack samples from those children. Although a similar pattern of mostly recessive causes was observed in the prenatal setting, the higher proportion of loss-of-function events in these cases was notable. The allelic series presented by the wealth of recessive variants greatly expanded the phenotypic expression of the respective genes. We also make important observations about dominant disorders; these observations include the pattern of de novo variants, the identification of 74 candidate dominant, disease-related genes, and the potential confirmation of 21 previously reported candidates. Finally, we describe the influence of a predominantly autosomal-recessive landscape on the clinical utility of rapid sequencing (Flash Exome). Our cohort’s genotypic and phenotypic data represent a unique resource that can contribute to improved variant interpretation through data sharing.

The chronic myeloproliferative neoplasms (CMPN) are a group of clonal hematopoietic stem cell disorders in which large numbers of red blood cells, white blood cells, or platelets grow and spread excess in the bone marrow and the peripheral blood. Cytogenetic analysis of the t(9;22) and molecular detection of BCR/ABL is the main diagnostic criteria in Philadelphia positive CMPN (CML). The identification of non-receptor tyrosine kinase JAK2 mutations (exon 14 JAK2 V617F and exon 12) have significantly contributed to our understanding of the molecular mechanisms in the pathogenesis of Philadelphia negative CMPN such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. According to the revised WHO classification, JAK2 mutation is considered as a major diagnostic and clonal marker in Philadelphia negative CMPN which will play a major role in designing personalized treatments for the disease. JAK2 V617F mutation frequency is unknown in Saudi Arabia. Therefore, investigation of the JAK2 V617F mutation was carried out in DNA samples from 78 peripheral blood specimens corresponding to patients with polycythemia vera (PV) (n = 11), Chronic myeloid leukemia (CML) (n = 45), essential thrombocythemia (ET) (n = 10), idiopathic myelofibrosis (MF) (n = 12). We used polymerase chain reaction and direct DNA sequencing to detect the JAK2 mutation. Overall, the incidence of the JAK2 V617F mutation was 91% in PV, 40% in ET, and 25% in MF. This approach proved to be reliable and more sensitive in detecting the mutation. Two essential findings arose from our study. First, this technique could be carried out with DNA samples, even partially degraded, from routinely processed BM or peripheral blood specimens. Second, after correlation with morphological features, it turned out that the characteristics of the megakaryocytes were more specific than the mutational status of JAK2 in characterizing ET and PMF. Concerning PV, as expected, the incidence of the JAK2 mutation was higher, but the morphological criteria were misleading in some cases, strongly suggesting that the combination of both morphology and molecular data would enable the characterization of virtually all cases. JAK2 V617F mutation frequency along with accurate morphological characterization is very reliable tool in diagnosing and classifying CMPN in Saudi patients.