Next Generation Sequencing Reveals Mutation Patterns and Prevalence of Inherited Renal Disease in Erbil City

Abstract

Background: Nephrotic syndrome and related renal disorders are significant health concerns globally, particularly in regions with high rates of consanguinity. Understanding the genetic landscape is crucial for improving diagnosis and treatment outcomes.
Aim: This study aimed to investigate the prevalence and characteristics of genetic mutations associated with inherited nephrotic syndromes in Erbil city, Kurdistan, to identify prevalent genetic variants and understand their clinical implications.
Materials and methods: A cohort of 100 patients presenting with nephrotic syndrome or related renal conditions underwent genetic analysis using Next-Generation Sequencing (NGS). Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results: The analysis revealed that NPHS2 was the most frequently affected gene, predominantly in homozygous form, underscoring its role in steroid-resistant nephrotic syndrome. Other significant mutations included SLC34A1 and VHL, associated with metabolic disturbances and syndromic renal disorders, respectively. Homozygous mutations comprised 70% of the detected variants, suggesting a notable impact of consanguinity. The majority of mutations were classified as pathogenic, with a significant number of Variants of Uncertain Significance (VUS) highlighting the need for further research. The findings emphasize the importance of genetic screening and counseling to improve early diagnosis and management of nephrotic syndrome and related conditions in regions with high consanguinity. Public health measures should include education on genetic risks and the promotion of genetic counseling to reduce the incidence of hereditary renal diseases. Further research is needed to clarify the clinical significance of VUS and expand genetic understanding through larger, diverse cohorts.