Scholarlink

<p>Genetic disease is often unrecognised. This study examined how often renal clinic patients, with a non-genetic diagnosis and without a family history of genetic disease recorded at the last three visits, had an underlying genetic form of kidney disease or diabetes. Sixty-four consecutive unrelated patients from a general nephrology clinic (44 male, 20 female) with a median age of 66&#xa0;years (range 26 – 87) underwent chart review and Whole Exome Sequencing (WES). WES results were filtered for rare disease-causing single nucleotide and copy number variants in genetic kidney disease (n = 495) and monogenic diabetes (n = 8) genes. The patients’ diagnoses included diabetes (n = 36, 56%), diabetic kidney disease (n = 28, 44%), autoimmune glomerulonephritis (n = 20,31%) or others (n = 12, 19%). Six (9%) volunteered a family history of genetic disease at recruitment. Twenty had at least one kidney cyst on imaging (20/59, 34%). Forty-four (69%) had an eGFR between 20 and 60&#xa0;ml/min/1.73m<sup>2</sup>, and 14 (22%) an eGFR &lt; 20&#xa0;ml/min/1.73m<sup>2</sup> or had undergone renal replacement therapy. Seven Pathogenic or Likely pathogenic variants (according to ClinVar) were found in 7 people (11%), in <i>COL4A3, CFH,</i> and <i>CHD7,</i> and 3 cystic kidney genes (<i>PKHD1</i> (n = 2), <i>SEC63, LRP5</i>). Three further individuals with diabetic kidney disease (3/36, 8%) had a possibly pathogenic variant (Likely pathogenic in one, and VUS in 2, in ClinVar) in a monogenic diabetes gene (<i>HNF1A, ABCC8, NEUROD1).</i> Pathogenic variants in a gene associated with kidney disease were identified in only three of the 6 patients with a positive family history. In conclusion,&#xa0;genetic variants associated with monogenic kidney disease occurred in possibly 11% (7/64) of renal clinic patients with a non-genetic diagnosis, and variants associated with monogenic diabetes in a further 9% (3/36) with diabetic kidney disease.</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

Monogenic kidney disease and monogenic diabetes are present in renal clinic patients with non-genetic diagnoses

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月15日

查看全文
  • Mary Huang,
  • Timothy Pianta,
  • David Barit,
  • Khalid Mahmood,
  • Deb Colville,
  • Heather Mack,
  • Judy Savige

摘要

Genetic disease is often unrecognised. This study examined how often renal clinic patients, with a non-genetic diagnosis and without a family history of genetic disease recorded at the last three visits, had an underlying genetic form of kidney disease or diabetes. Sixty-four consecutive unrelated patients from a general nephrology clinic (44 male, 20 female) with a median age of 66 years (range 26 – 87) underwent chart review and Whole Exome Sequencing (WES). WES results were filtered for rare disease-causing single nucleotide and copy number variants in genetic kidney disease (n = 495) and monogenic diabetes (n = 8) genes. The patients’ diagnoses included diabetes (n = 36, 56%), diabetic kidney disease (n = 28, 44%), autoimmune glomerulonephritis (n = 20,31%) or others (n = 12, 19%). Six (9%) volunteered a family history of genetic disease at recruitment. Twenty had at least one kidney cyst on imaging (20/59, 34%). Forty-four (69%) had an eGFR between 20 and 60 ml/min/1.73m2, and 14 (22%) an eGFR < 20 ml/min/1.73m2 or had undergone renal replacement therapy. Seven Pathogenic or Likely pathogenic variants (according to ClinVar) were found in 7 people (11%), in COL4A3, CFH, and CHD7, and 3 cystic kidney genes (PKHD1 (n = 2), SEC63, LRP5). Three further individuals with diabetic kidney disease (3/36, 8%) had a possibly pathogenic variant (Likely pathogenic in one, and VUS in 2, in ClinVar) in a monogenic diabetes gene (HNF1A, ABCC8, NEUROD1). Pathogenic variants in a gene associated with kidney disease were identified in only three of the 6 patients with a positive family history. In conclusion, genetic variants associated with monogenic kidney disease occurred in possibly 11% (7/64) of renal clinic patients with a non-genetic diagnosis, and variants associated with monogenic diabetes in a further 9% (3/36) with diabetic kidney disease.