Scholarlink

Background <p>Congenital abnormalities of the kidney and urinary tract (CAKUT) are the leading cause of pediatric end-stage renal disease, affecting 3–6 per 1,000 live births. Genetic mutations underlie approximately 30% of cases, necessitating next-generation sequencing for precise diagnosis.</p> Aims <p>This study aims to identify the genetic etiology of CAKUT within a cohort of ten Egyptian patients (mean age 6.38 ± 3.52 years) presenting with diverse phenotypes, including renal agenesis, hypoplasia, and ureteric anomalies.</p> Materials and methods <p>Patients underwent comprehensive clinical evaluation, including pedigree construction, ultrasonography, and scintigraphy. Solo whole-exome sequencing (WES) was performed to identify underlying variants. Candidate variants were correlated with phenotypes and validated via Sanger sequencing, with pathogenicity assessed according to ACMG guidelines.</p> Results <p>WES identified ten disease-associated variants across eight genes. Key findings include a novel heterozygous likely pathogenic frameshift variant (c.651delA: p.S217fs) in <i>RIT1</i>, causing Noonan syndrome type 8 (NS-8) in a patient with unilateral renal atrophy. Additional variants included a heterozygous <i>COL4A3</i> VUS (Alport syndrome), a <i>REN</i> VUS (autosomal dominant tubulointerstitial kidney disease), and biallelic <i>CLCNKB</i> variants (Bartter syndrome type 3). Genetic signatures were also identified in <i>PKD1</i>,<i> PKHD1</i>,<i> FRAS1</i>, and <i>WNT9B</i>.</p> Conclusion <p>WES is a high-yield diagnostic tool for CAKUT. This study provides the first report of a <i>RIT1</i> mutation in Egypt and the first confirmed association of <i>RIT1</i> with renal anomalies in NS-8. Expanding genomic screening and incorporating copy number variant (CNV) analysis are essential to fully define the mutation spectrum and improve clinical management for Egyptian CAKUT patients.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Clinical and Molecular characteristics of kidney and urinary tract congenital anomalies in a cohort of Egyptian patients using whole-exome sequencing

  • 期刊论文

  • 发表日期：

    2026年5月14日

查看全文
  • Tamer H.A. Ammar,
  • Heba Mostafa Ahmed,
  • Eman E.A. Mohammed,
  • Hazem Mohamed El-Hariri,
  • Alice Abdelaleem,
  • Manal M. Thomas

摘要

Background

Congenital abnormalities of the kidney and urinary tract (CAKUT) are the leading cause of pediatric end-stage renal disease, affecting 3–6 per 1,000 live births. Genetic mutations underlie approximately 30% of cases, necessitating next-generation sequencing for precise diagnosis.

Aims

This study aims to identify the genetic etiology of CAKUT within a cohort of ten Egyptian patients (mean age 6.38 ± 3.52 years) presenting with diverse phenotypes, including renal agenesis, hypoplasia, and ureteric anomalies.

Materials and methods

Patients underwent comprehensive clinical evaluation, including pedigree construction, ultrasonography, and scintigraphy. Solo whole-exome sequencing (WES) was performed to identify underlying variants. Candidate variants were correlated with phenotypes and validated via Sanger sequencing, with pathogenicity assessed according to ACMG guidelines.

Results

WES identified ten disease-associated variants across eight genes. Key findings include a novel heterozygous likely pathogenic frameshift variant (c.651delA: p.S217fs) in RIT1, causing Noonan syndrome type 8 (NS-8) in a patient with unilateral renal atrophy. Additional variants included a heterozygous COL4A3 VUS (Alport syndrome), a REN VUS (autosomal dominant tubulointerstitial kidney disease), and biallelic CLCNKB variants (Bartter syndrome type 3). Genetic signatures were also identified in PKD1, PKHD1, FRAS1, and WNT9B.

Conclusion

WES is a high-yield diagnostic tool for CAKUT. This study provides the first report of a RIT1 mutation in Egypt and the first confirmed association of RIT1 with renal anomalies in NS-8. Expanding genomic screening and incorporating copy number variant (CNV) analysis are essential to fully define the mutation spectrum and improve clinical management for Egyptian CAKUT patients.