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2,200 previously unpublished Saudi families as a first-tier test.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.

No abstract

Introduction: Studies have shown that pulmonary exacerbations in cystic fibrosis (CF) patients are associated with respiratory viruses. The most common agent causing viral infections in patients with CF before the age of 3 years is respiratory syncytial virus. Objectives: To obtain the prevalence of the different types of viral infection in CF patients and to identify its relation with the type of bacterial infection, (CFTR) mutations and pulmonary function test (PFT). Methodology: A retrospective charts review of 387 patients with CF of all age groups who were screened for the detection of viruses during respiratory exacerbation from the period of January 1,1984 to June 1, 2016. Results: A total of 159 CF patients had pulmonary exacerbation and had viral PCR obtained. Fifty-eight patients (36%) had positive viral PCR. Males were more commonly infected in 30/58 patients (52%) compared to females in 28 patients (48%). Forty-five of 58 patients (78%) were alive and 13 patients (22%) died. Rhinovirus was the most frequently reported viral PCR in 33/74 sample (45%). Out of 74 viral PCR, 41 (55.4%) were during the colder seasons (October–February) and 33 (44.5%) during the warmer seasons (March–September). During viral infection and viral recurrence, there was an increase in bacterial colonization specifically of H. influenza and staphylococcus aureus. The most common CFTR mutation for the CF viral infection is: 3120+1G>A in Intron 16 in 11/57 patients (19%). The Eastern Province had the highest viral infection of 24 out of 57 patients (42%). Follow-up PFT post viral infection showed no significant difference in the type and the severity of PFT compared to the initial PFT during the viral illness. Conclusion: Viral infections contributed to the increase in morbidity and mortality of CF patients in our population, and rhinovirus was the most common causative agent. Viral infections and viral recurrence increased the prevalence of bacterial infection of specific pathogens such as H. in fluenza and S. aureus. Physicians should be aware to prevent progressive lung damage in CF patients by treating the concomitant viral and bacterial infections. Viral infection may be associated with some common CFTR mutations.

No abstract

Background"Bounce back" patients is a term used to refer to patients returning to the emergency department within 72 hours after the first visit. This can be attributed to various factors related to diagnosis, management, or the health care system. ObjectiveThis study sought to evaluate the extent of bounce-back patients in the emergency department of King Abdullah Medical City (KAMC), Makkah, Saudi Arabia, and then explore the possible relationship between shock index (SI) and bounce-back patients. MethodsThis is a retrospective chart review of the electronic system among patients who have returned to the emergency department within 72 hours from the index visit. All records were reviewed from May 2019 to May 2021. Vital signs were collected to calculate the shock index (heart rate/systolic blood pressure). The data were analyzed by SPSS Statistics v.27.0 (IBM Corp., Armonk, NY). ResultsA total of (506) responses were analyzed. The median age was 56 years with an IQR of 40-67, and males represented 55.3%. Around three-quarters of the second complaints (76.9%) were related to the index visit. The durations between the visits were as follows: 51.8% within 24 hours, 30.2% within 25-48 hours, and 18% within 49-72 hours. The median and IQR for shock index were 0.67 and 0.59-0.80 respectively, while the median and IQR for reverse shock index were 1.49 and 1.25-1.71 respectively. Diabetes and the duration between the two visits were associated with the complaints (p-value=0.005, p-value=0.011) respectively. ConclusionThe majority of bounce-back cases occurred within the first 24 hours in our sample. Hypertension, diabetes, and ischemic heart diseases were the most prevalent comorbidities among the bounce-back patients. The majority of bounce-back patients (76.9%) presented with complaints related to the index visit.