Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56) families, 54 of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13), MYO7A (11), SLC26A4 (10), TMPRSS3 (9), TMC1 (8), ILDR1 (6), and CDH23 (4). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56 of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371. © American College of Medical Genetics and Genomics

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p<0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p<0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved

First report of citrus yellow vein clearing virus infecting new natural host plants in Turkey

[No abstract available

Electrical stimulation of wrist and fingers for sensory and functional recovery in acute hemiplegia

Objective: To investigate the effects of a short-term electrical stimulation in conjunction with neurodevelopmental exercises on sensory and functional recovery of hemiparetic upper limb in acute stroke patients

Detection of citrus tristeza virus (CTV) from satsuma owari mandarins (citris unshiu) by direct tissue blot immunoassay (DTBIA), das-elisa, and biological indexing

Three different citrus-producing regions of Turkey—Edremit Gulf, Coastal Aegean, and eastern Black Sea—were surveyed in 2005 and 2006. A total of 119 samples were collected from Satsuma Owari mandarin (Citrus unshiu) trees grafted on Citrus tristeza virus (CTV)-resistant Poncirus trifoliata rootstocks in commercial groves and home gardens. All samples were tested for the presence of CTV by direct tissue blot immunoassay (DTBIA) and double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) using young shoots. The samples that tested positive were indexed for biological properties. The results obtained from DTBIA tests showed that 20 of 119 (16.8%) tested trees were infected with CTV and 99 trees were virus free. All samples that tested positive in DTBIA were also positive in DAS-ELISA. After biological indexing, none of these 20 isolates showed any symptoms on sour orange, grapefruit, and sweet orange plants, but all isolates induced vein-clearing symptoms on Mexican lime (Citrus aurantifoli) in 9 months. Some isolates also caused leaf-cupping and chlorosis in Mexican lime. However, 15 months after initial grafting, all isolates induced mild to moderate stem-pitting on Mexican lime. In addition, young tissues, petioles, and leaf samples were collected periodically at monthly intervals for 1 year (2006) from a 25-year-old Satsuma Owari mandarin grafted on P. trifoliata in the Edremit Gulf. CTV was readily detected in tissue blots of young shoots and petioles from CTV-infected plants during the autumn, winter, and spring seasons. Similarly, the highest ELISA values were obtained in April; the lowest values were noted in September. This study showed that DTBIA is a rapid, sensitive, and reliable procedure for detecting CTV under field conditions. © 2008 Taylor & Francis Group, LLC.This work was supported by Grant no. 1040129 from the Scientific andTechnological Research Council of Turkey (TUBITAK)