BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10−14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)

Aim To determine the prognostic value of cell cycle regulators cyclin D1 and p27 for papillary thyroid carcinomas.Methods Analysis included 180 patients with papillary thyroid carcinoma who underwent surgery at Split University Hospital Center between 1999 and 2001. Clinical data were obtained from clinical charts and histopathology reports. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue by antibody p27 and cyclin D1. Quantification was based on the intensity and distribution of nuclear staining.Results Univariate analysis showed that sex (P = 0.019) and capsular invasion (P = 0.010) were significant predictors of lymph node metastases, whereas age (P = 0.96), histopathological variant (P = 0.075), size (P = 0.556) and multifocality (P = 0.131) were not. Univariate analysis also showed that overexpression of cyclin D1 (P < 0.001) and underexpression of p27 (P < 0.001) predicted lymph node metastases in papillary thyroid carcinomas. There was a significant correlation between cyclin D1 (P = 0.024) and p27 (P = 0.029) expression in two prognostic groups of low and high risk. Low risk group was cyclin D1 negative and p27 positive, whereas high risk group was cyclin D1 positive and p27 negative. Multivariate analysis confirmed that sex (P = 0.041), capsular invasion (P = 0.027), and p27 (P < 0.001) were strong independent predictors of lymph node metastases in the high-risk group.Conclusions Immunohistochemical analysis of p27 expression may be a valuable tool for identifying risk of lymph node metastases and more aggressive behavior of papillary thyroid carcinoma.

Objectives: To examine seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in industry workers population sample. Methods: From 23 to April 28, 2020, we conducted serological testing for antibodies (Immunoglobulin G (IgG) and Immunoglobulin M (IgM)) on 1494 factory employees living in the Split-Dalmatia and Šibenik-Knin County (Croatia). Results: We detected antibodies in 1.27% of participants (95% confidence interval [CI] 0.77–1.98%). In Split facility 13/1316 (0.99%, 95% CI 0.53–1.68%) of participants were tested positive, of which 13/1079 (1.20%, 95% CI 0.64–2.05%) of those living outside the facility and 0/237 (0%, 95% CI 0–1.26%) of those living inside the facility. In Knin facility, 6/178 (3.37%, 95% CI 1.25–7.19%) participants were tested positive for antibodies. Conclusions: The study showed relatively small SARS-CoV-2 antibody seroprevalence in the DIV Group population sample.