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Polycystic kidney diseases (PKDs) comprise the most common Mendelian forms of renal disease. It is characterised by the development of fluid-filled renal cysts, causing progressive loss of kidney function, culminating in the need for renal replacement therapy or kidney transplant. Ireland represents a valuable region for the genetic study of PKD, as family sizes are traditionally large and the population relatively homogenous. Studying a cohort of 169 patients, we describe the genetic landscape of PKD in Ireland for the first time, compare the clinical features of patients with and without a molecular diagnosis and correlate disease severity with autosomal dominant pathogenic variant type. Using a combination of molecular genetic tools, including targeted next-generation sequencing, we report diagnostic rates of 71-83% in Irish PKD patients, depending on which variant classification guidelines are used (ACMG or Mayo clinic respectively). We have catalogued a spectrum of Irish autosomal dominant PKD pathogenic variants including 36 novel variants. We illustrate how apparently unrelated individuals carrying the same autosomal dominant pathogenic variant are highly likely to have inherited that variant from a common ancestor. We highlight issues surrounding the implementation of the ACMG guidelines for variant pathogenicity interpretation in PKD, which have important implications for clinical genetics.

Background: Intussusception in adult patients is uncommon and appendiceal lead points are particularly rare., Case Presentation: We present the case of a 42-year-old male with a history of ulcerative colitis, presenting with sudden onset abdominal pain and bloody diarrhoea. Endoscopy revealed grossly normal mucosa in the descending colon with a congested polypoid mass in the proximal transverse colon. Computed tomography revealed ileocecal intussusception at the hepatic flexure. A right hemicolectomy was performed, where a grossly dilated appendix was noted, resected and sent for histopathological evaluation. Results revealed low-grade appendiceal mucinous neoplasm. Post-operatively, the patient remained symptom free, however required reintroduction of biologic therapy due to relapse of his ulcerative colitis 12 weeks later., Conclusion: This case depicts a rare acute surgical presentation and reminds physicians and surgeons of the importance of 'thinking outside the box' in clinical practice.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). We aimed to compare renal transplant outcomes in people with ESRD due to ADTKD to those with other causes of renal failure., Methods: Patients with clinical characteristics consistent with ADTKD by the criteria outlined in the 2015 KDIGO consensus were included. We compared ADTKD transplant outcomes with those of 4633 non-ADTKD renal transplant recipients., Results: We included 31 patients who met diagnostic criteria for ADTKD in this analysis, 23 of whom had an identified mutation (28 were categorized as definite-ADTKD and 3 as suspected ADTKD). Five patients received a second transplant during follow-up. In total, 36 grafts were included. We did not identify significant differences between groups in terms of graft or patient survival after transplantation. Twenty-five transplant biopsies were performed during follow-up, and none of these showed signs of recurrent ADTKD post-transplant., Conclusion: In patients with ESRD due to ADTKD, we demonstrate that transplant outcomes are comparable with the general transplant population. There is no evidence that ADTKD can recur after transplantation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN , and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.