Genome sequencing in families with congenital limb malformations

The extensive clinical and genetic heterogeneity of congenital limb malformation calls for comprehensive genome-wide analysis of genetic variation. Genome sequencing (GS) has the potential to identify all genetic variants. Here we aim to determine the diagnostic potential of GS as a comprehensive one-test-for-all strategy in a cohort of undiagnosed patients with congenital limb malformations. We collected 69 cases (64 trios, 1 duo, 5 singletons) with congenital limb malformations with no molecular diagnosis after standard clinical genetic testing and performed genome sequencing. We also developed a framework to identify potential noncoding pathogenic variants. We identified likely pathogenic/disease-associated variants in 12 cases (17.4%) including four in known disease genes, and one repeat expansion in HOXD13. In three unrelated cases with ectrodactyly, we identified likely pathogenic variants in UBA2, establishing it as a novel disease gene. In addition, we found two complex structural variants (3%). We also identified likely causative variants in three novel high confidence candidate genes. We were not able to identify any noncoding variants. GS is a powerful strategy to identify all types of genomic variants associated with congenital limb malformation, including repeat expansions and complex structural variants missed by standard diagnostic approaches. In this cohort, no causative noncoding SNVs could be identified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00439-021-02295-y

Fibrous pleural plaques detected at autopsy

The reported case was a 84-year-old male, dead after a traffic accident. The death was considered to be suspicious by prosecutor and an autopsy was mandated. In macroscopic autopsy investigation left tibia, fibula and multiple rib fractures, widespread seborrheic keratoses, and hyperpigmented skin lesions were detected. In the left chest cavity blood content and white colored lesions spread on the left parietal pleura and chest surface of the thoracic diaphragm were observed. The histological examination of the pleural lesions revealed fibrotic hyalinized structures with calcified foci. Investigation of pleural plaques in forensic autopsy is important for scientific classification of this interesting entity

Us-Guided Botulinum Toxin Injection For Excessive Drooling In Children

PURPOSE We aimed to evaluate the safety and efficacy of botulinum toxin A (BTX-A) injections under ultrasonography (US) guidance for children with excessive drooling. MATERIALS AND METHODS Between January 2006 and January 2011,44 BTX-A injections into bilateral submandibular glands were performed in 20 children (mean age, 9.1 years; ran e, 3-16 years; gender, 151 boys and 5 girls) under intravenous Sedation. Efficacy of the injections was evaluated 4-12 weeks after the injection. Severity of drooling was assessed using the Teacher Drooling Scale (TDS). If the patient or the patient's caregiver reported a good initial response, injections were then repeated periodically when drooling reached the preinjection score. If there was no response or suboptimal response, a booster injection of BTX-A was given after one month. RESULTS Technical success rate was 100%. No procedure-related major or minor complication was detected. One family (5%) reported intermittent problems with swallowing due to viscous saliva. A successful outcome was defined as a minimum two point reduction in TDS score. This outcome occurred. for 8 of 20 patients four weeks after the first injection. After consecutive sessions, clinical success was achieved at the end of the 12 weeks for 16 patients (80%). The mean TDS score decreased from 4.75 to 2.1 at the end of the study for all patients (P < 0.05). Four patients did not respond to BTXA injection. Submandibular resection was applied to 3 of 4 unresponsive patients. Two patients had complete remission after surgery, but one patient showed excessive drooling that could not be controlled. CONCLUSION US-guided submandibular BTX-A injection is a safe and effective procedure in treating drooling in children. It can be performed under intravenous sedation and does not require general anesthesia

Ecstasy Intake Related Coagulopathy

3,4-methylenedioxymethamphetamine (MDMA), substance known as "Ecstasy" among the people and used due to entertainment, euphoric and energy booster effect, is one of the famous synthetic stimulants.&nbsp; 22-year-old man was found as unconscious in the early morning. According to the expressions of his family and friends, it was learned that he drank alcohol until late in the previous evening and took ecstasy besides this before he died. It was reported that he was taken to intensive care unit with temperature of 41oC and death occurred 12 hours later. At autopsy in external examination, petechial and purpuric hemorrhages in purple and red color were detected on body. In internal examination, petechial hemorrhages on the surface of the heart and lungs, subendocardial hemorrhage in the heart, hemorrhage on the mucosal surface of the stomach were seen. In the toxicological analyses of the blood, Paracetamol (4870 ng/ml), MDMA (847 ng/ml), MDA (94,2 ng/ml), Lidocaine (23 ng/ml), Pantoprazole (10,5 ng/ml), Midazolam (1,83 ng/ml) were detected. The death occurred due to coagulopathy related MDMA intoxication. Here, we present a case of autopsy, clinical findings and histopathologic findings, laboratory results in medicolegal literature

Glial fibrillary acidic protein (GFAP) and CD34 expression in the human optic nerve and brain in methanol toxicity

Introduction: The toxicity of methanol is as a result of its metabolites, formaldehyde and formic acid. Formic acid induces severe metabolic acidosis causing death, and is the primary agent responsible for ocular toxicity. Glial fibrillary acidic protein ( GFAP) immunostaining is the most commonly used method for examining astrocyte proliferation and hypertrophy after various central nervous system injuries. The antigen CD34 is expressed widely on vascular endothelium, including that of the central nervous system and high endothelial venules

Forensic age estimation in living individuals by 1.5T magnetic resonance imaging of the knee: a retrospective MRI study

Our aim is to analyse proximal tibial epiphysis and distal femoral epiphysis patterns according to the Dedouit staging method using 1.5 T magnetic resonance imaging (MRI) with fast spin echo (FSE) for proton density images. In addition, we discuss the results in relation to the literature for forensic age estimation. In this study, images belonging to 195 female and 277 male patients ranging in age from 10 to 30 years who had a knee MRI for any reason in our Radiology Clinic between January 2014 and December 2016 were retrospectively evaluated. According to the Dedouit et al. five-stage method, they were evaluated by two radiologists. The kappa value was calculated for intra-observer and inter-observer compliance. The evaluation of knee epiphysis patterns from MRI is an alternative, efficient, radiation-free and non-invasive method that is helpful in forensic age estimation. In particular, stage 5 in distal femoral epiphysis can determine the 21st year of life in both sexes, and proximal tibial epiphysis could present evidence of age 18 in males. It should be used for evaluation in addition to other methods for determining skeletal system maturity.WOS:0005448927000082-s2.0-8505761476

Unusual autopsy finding: Simon's bleeding

Objective: To determine whether or not hanging had taken place before or after the death of the victim is quite important in the identification of criminal cases pretended to be suicidal attempts

Unusual autopsy finding: Simon's bleeding

Objective: To determine whether or not hanging had taken place before or after the death of the victim is quite important in the identification of criminal cases pretended to be suicidal attempts

Occult papillary thyroid carcinoma: prevalence at autopsy in Turkish people

The epidemiological features of occult papillary thyroid carcinoma (OPTC) at autopsy have not previously been reported in Turkish people. This study provides data on the prevalence of OPTC in people from the Marmara region in Turkey. The study includes thyroid glands from 93 male and 15 female cadavers between 18 and 80 years of age. The thyroid glands were removed, fixed and sectioned at 2-mm intervals. The sections were stained with hematoxylin and eosin, and were examined by a single pathologist. A total of 108 thyroid glands were examined. Macroscopic lesions were found in 36 (33.3%) glands (95% confidence interval = 24-42). OPTC was found in four (3.7%) cases (95% confidence interval = 1.0-7.5). It was concluded that in the Turkish people from the Marmara region, the prevalence of OPTC found at autopsy was relatively low. No age or sex predilection was detected. European Journal of Cancer Prevention 20:308-312 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins