Exome sequencing and case–control analyses identify RCC1 as a candidate breast cancer susceptibility gene

Breast cancer is a genetic disease but the known genes explain a minority of cases. To elucidate the molecular basis of breast cancer in the Tunisian population, we performed exome sequencing on six BRCA1/BRCA2 mutation‐negative patients with familial breast cancer and identified a novel frameshift mutation in RCC1, encoding the Regulator of Chromosome Condensation 1. Subsequent genotyping detected the 19‐bp deletion in additional 5 out of 153 (3%) breast cancer patients but in none of 400 female controls (p = 0.0015). The deletion was enriched in patients with a positive family history (5%, p = 0.0009) and co‐segregated with breast cancer in the initial pedigree. The mutant allele was lost in 4/6 breast tumors from mutation carriers which may be consistent with the hypothesis that RCC1 dysfunction provides a selective disadvantage at the stage of tumor progression. In summary, we propose RCC1 as a likely breast cancer susceptibility gene in the Tunisian population.     

Bactériémies à bactéries multirésistantes chez les greffés de cellules souches-hématopoïétiques

Background:

Bacteremia become fearsome in hematopoietic stem cell transplant (HSCT) recipients with the emergence of multidrug-resistant (MDR) strains.

Aim:

Our purpose was to investigate the prevalence of MDR bacteremia in HSCT recipients at the Tunisian National Bone Marrow Transplant Center, associated factors and attributable mortality rate.

Methods:

Our retrospective study (January 2010-December 2017) included all MDR bacteremia in the Hematology department. MDR rods were: extended spectrum beta-lactamase producing Enterobacterales (ESBL-E), P. aeruginosa and A. baumannii resistant to at least three families of antibiotics, methicillin-resistant S. aureus (MRSA) and vancomycin resistant E. faecium (VRE).

Results:

The prevalence of MDR bacteremia among HSCT recipients was 5.9% (48/816) with a stable trend over time (rs=0.18). Neutropenia, prior hospitalization, prior antibiotherapy and prior colonization with MDR pathogens were observed in 59%, 58%, 48% and 31% of cases, respectively. Imipenem was the most prescribed first-line antibiotic (50%). The attributable mortality rate was 13%. MDR bacteria (n=48) belonged to ESBL-E (60%), P. aeruginosa (19%), A. baumannii (13%), MRSA (4%) and VRE (4%). For ESBL-E and P. aeruginosa, the rates of antibiotic resistance were respectively, 17% and 44% to imipenem, 31% and 56% to amikacin and 15% and 0% to colistin. Strains of A. baumannii were susceptible only to colistin. The MRSA (n=2) were resistant to ciprofloxacin and gentamicin and susceptible to glycopeptides. The VRE (n=2) were susceptible to linezolid and tigecycline.

Conclusion:

Low prevalence of MDR bacteremia in HSCT recipients but high attributable mortality rate, requiring reinforcement of hygiene measures.     

Estimation of Recent and Ancient Inbreeding in a Small Endogamous Tunisian Community Through Genomic Runs of Homozygosity

Runs of homozygosity (ROHs) are extended genomic regions of homozygous genotypes that record populations’ mating patterns in the past. We performed microarray genotyping on 15 individuals from a small isolated Tunisian community. We estimated the individual and population genome‐wide level of homozygosity from data on ROH above 0.5 Mb in length. We found a high average number of ROH per individual (48.2). The smallest ROH category (0.5–1.49 Mb) represents 0.93% of the whole genome, while medium‐size (1.5‐4.99 Mb) and long‐size ROH (≥5 Mb) cover 1.18% and 0.95%, respectively. We found that genealogical individual inbreeding coefficients (F_ped) based on three‐ to four‐generation pedigrees are not reliable indicators of the current proportion of genome‐wide homozygosity inferred from ROH (F_ROH) either for 0.5 or 1.5 Mb ROH length thresholds, while identity‐by‐descent sharing is a function of shared coancestry. This study emphasizes the effect of reproductive isolation and a prolonged practice of consanguinity that limits the genetic heterogeneity. It also provides evidence of both recent and ancient parental relatedness contribution to the current level of genome‐wide homozygosity in the studied population. These findings may be useful for evaluation of long‐term effects of inbreeding on human health and for future applications of ROHs in identifying recessive susceptibility genes.     

Radiological features of Adenomatoid odontogenic tumor: Report of a maxillary case and a mandibular one

We present two cases of AOT, the first case concerns a 23‐year‐old patient with an AOT located in the maxilla and the second case involves a 37‐year‐old patient presenting an AOT with mandibular localization.     

Elderly-onset adult Still’s disease

Adult-onset Still’s disease is a rare inflammatory disorder usually affecting young adults. Elderly-onset Still’s disease (EOSD) is reported in some cases, commonly in Japan, the USA and Europe. One of the most commonly used criteria for diagnosing EOSD is Yamaguci criteria. In elderly patients more severe course of the disease and more complications may be expected than in the younger group of patients with Still’s disease. The lungs involvement is rather rare manifestation of this disease. In our article we discuss the problem of both the development of Still’s disease in the elderly and interstitial lung changes in the course of the disease, based on available literature and own cases from one centre.     

Annual costs associated with diagnosis of uterine leiomyomata

OBJECTIVE: To describe the annual care, direct health care, and indirect work loss costs for women with a diagnosis of uterine leiomyomata. METHODS: We examined data from an employer claims database of 1.2 million beneficiaries (1999 to 2003). Analysis was restricted to women with at least 12 months of continuous coverage and ages 18 to 64 years with at least one diagnosis of leiomyomata (International Classification of Diseases, 9th Revision, 218.xx, 654.1x). We selected a comparison group of women without a leiomyoma diagnosis using a 1:1 match on age, employment, region, health plan type, and length of enrollment. We compared resource use, disability claims, and excess costs in the year after the index diagnosis. RESULTS: The average age of women diagnosed with leiomyomata in this study was 43.7 years. Women with leiomyomata (N = 5,122) had more clinic visits (relative risk [RR] 1.2, 95% confidence interval [CI] 1.2-1.2), diagnostic tests (RR 3.1, 95% CI 2.9-3.2), and procedures (RR 34.6, 95% CI 25.8-46.5) than controls (N = 5,122). Within 1 year of the diagnosis of leiomyomata, 42% of women had a complete blood count, 66% had pelvic imaging, and 30% had surgery (68% of surgical procedures involved hysterectomy). Women with leiomyomata were 3-fold more likely to have disability claims (RR 3.1, 95% CI 2.7-3.6). Estimated average annual excess cost for each woman with leiomyomata (adjusted for confounders) was Dollars 4,624 (Dollars 771 in work loss costs). Total costs for women with leiomyomata were 2.6 times greater than for controls. CONCLUSION: Diagnosed uterine leiomyomata are associated with increased resource use and with substantially higher health care and work loss costs. LEVEL OF EVIDENCE: II-3.     

Erythematous nodule of the eyelid

A 68-year-old woman had a 15-day history of a well-circumscribed, erythematous nodule of the left eyebrow/eyelid area. After excision a primary cutaneous large B-cell lymphoma was diagnosed. The tumor was excised with clear margins and the patient has shown no recurrence over two years.     

Intravitreal injection of triamcinolone combined with bevacizumab for choroidal neovascularization associated with large retinal pigment epithelial detachment in age-related macular degeneration

Purpose  

To discuss the effect and outcome of a combined intravitreal triamcinolone acetonide (IVTA) injection with intravitreal bevacizumab (IVB) in treating choroidal neovascularization (CNV) associated with large retinal pigment epithelial detachment (PED) in age-related macular degeneration (AMD).