BackgroundThe molecular basis of heterotaxy and congenital heart malformations associated with disruption of left–right asymmetry is broad and heterogenous, with over 25 genes implicated in its pathogenesis thus far.ObjectiveWe sought to elucidate the molecular basis of laterality disorders and associated congenital heart defects in a cohort of 30 unrelated probands of Arab–Muslim descent, using next-generation sequencing techniques.MethodsDetailed clinical phenotyping followed by whole-exome sequencing (WES) was pursued for each of the probands and their parents (when available). Sanger sequencing was used for segregation analysis of disease-causing mutations in the families.ResultsUsing WES, we reached a molecular diagnosis for 17 of the 30 probands (56.7%). Genes known to be associated with heterotaxy and/or primary ciliary dyskinesia, in which homozygous pathogenic or likely pathogenic variants were detected, included CFAP53 (CCDC11), CFAP298 (C21orf59), CFAP300, LRRC6, GDF1, DNAAF1, DNAH5, CCDC39, CCDC40, PKD1L1 and TTC25. Additionally, we detected a homozygous disease causing mutation in DAND5, as a novel recessive monogenic cause for heterotaxy in humans. Three additional probands were found to harbour variants of uncertain significance. These included variants in DNAH6, HYDIN, CELSR1 and CFAP46.ConclusionsOur findings contribute to the current knowledge regarding monogenic causes of heterotaxy and its associated congenital heart defects and underscore the role of next-generation sequencing techniques in the diagnostic workup of such patients, and especially among consanguineous families.
As genetic testing becomes more available, its utilization as an early diagnostic tool in nephrology is more common. The objective of the study is to examine diagnostic agreement between the renal biopsy findings and genetic diagnoses. A retrospective study was conducted in February 2022. A total of 28 patients had both genetic diagnosis and histologic results (n = 1 nephrectomy, n = 27 biopsy). We collected clinical, renal biopsy findings, and genetic information. The relationship between the histologic findings and the genetic diagnoses was classified as: concordant, nonspecific, and discordant. A total of 15 males and 13 females were included (mean age = 9.6 years). Clinical suspicion of Alport syndrome was the most common reason for referral (n = 11, 39.3%), followed by nephrotic syndrome (n = 8, 28.5%), "other" (n = 6, 21.4%), cystic kidney disease (n = 1, 3.6%), isolated hematuria (n = 1, 3.6%), and non-nephrotic proteinuria (n = 1, 3.6%). The overall concordance rate between renal histologic and genetic diagnoses was 71.4% (20/28), nonspecific biopsy results were observed in 17.9% (5/28), and discordant results were observed in 10.7%(3/28). All patients referred for suspected Alport Syndrome had pathogenic/likely
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.