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Abstract <p>Nail–patella syndrome (NPS) is an autosomal dominant disorder caused by <i>LMX1B</i> mutations and typically associated with glomerular proteinuria. We report three brothers carrying a maternally inherited heterozygous <i>LMX1B</i> mutation (NM_001174147.2: c.309C &gt; G (p.Cys103Trp)), all presenting with classical skeletal features of NPS. Two siblings developed early-onset proteinuria predominantly composed of low-molecular-weight proteins, hypercalciuria, and ophthalmologic abnormalities including cataracts and glaucoma; one also exhibited nephrocalcinosis. Further genetic analysis identified a hemizygous <i>OCRL</i> pathogenic mutation (NM_000276.4: c.2209G &gt; A (p.Glu737Lys)) in the two affected brothers but not in the third sibling, who had no renal involvement. This intrafamilial discordance supports a dual genetic diagnosis. Our findings emphasize the importance of reconsidering the initial diagnosis when clinical features are atypical and highlight the value of comprehensive genetic testing in patients with unusual renal presentations.</p>

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Atypical renal phenotype with tubular proteinuria and hypercalciuria in siblings with nail–patella syndrome: evidence for a dual genetic diagnosis

  • 期刊论文

  • 发表日期：

    2026年7月3日

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  • Geneviève Benoit,
  • Philippe M. Campeau,
  • Mélissa Fiscaletti,
  • Valancy Miranda,
  • Camille Laroche,
  • Alexandra Cambier

摘要

Abstract

Nail–patella syndrome (NPS) is an autosomal dominant disorder caused by LMX1B mutations and typically associated with glomerular proteinuria. We report three brothers carrying a maternally inherited heterozygous LMX1B mutation (NM_001174147.2: c.309C > G (p.Cys103Trp)), all presenting with classical skeletal features of NPS. Two siblings developed early-onset proteinuria predominantly composed of low-molecular-weight proteins, hypercalciuria, and ophthalmologic abnormalities including cataracts and glaucoma; one also exhibited nephrocalcinosis. Further genetic analysis identified a hemizygous OCRL pathogenic mutation (NM_000276.4: c.2209G > A (p.Glu737Lys)) in the two affected brothers but not in the third sibling, who had no renal involvement. This intrafamilial discordance supports a dual genetic diagnosis. Our findings emphasize the importance of reconsidering the initial diagnosis when clinical features are atypical and highlight the value of comprehensive genetic testing in patients with unusual renal presentations.