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Background <p>Congenital nephrotic syndrome (CNS) is a rare disorder caused by mutations in genes essential for podocyte function and glomerular slit diaphragm integrity, including <i>CRB2</i> (Crumbs Cell Polarity Complex Component 2). <i>CRB2</i> mutations are linked to focal segmental glomerulosclerosis and ventriculomegaly with cystic kidney disease, but their full phenotypic spectrum remains unclear. We describe the clinical course of monozygotic twins with a homozygous <i>CRB2</i> mutation, highlighting severe complications following kidney transplantation.</p> Methods <p>The twins, who were followed and managed throughout their clinical course, were diagnosed with CNS after prenatal suspicion of polycystic kidney disease. Initial exome sequencing was negative, but subsequent whole exome sequencing revealed a homozygous <i>CRB2</i> variant.</p> Results <p>Both twins presented with CNS, requiring intensive supportive care. Additional findings included cerebral heterotopia, cardiac involvement, and developmental delay. They both progressed to kidney failure, necessitating hemodialysis in early childhood. Post-transplant, the first twin succumbed to a systemic fungal infection, while the second developed complications linked to immune dysregulation, including post-transplant lymphoproliferative disease (PTLD), immune thrombocytopenic purpura (ITP), multiple viremias, and de novo donor-specific antibodies (DSA).</p> Conclusions <p>This case expands the phenotypic spectrum of <i>CRB2</i>-related disease, highlights management challenges, and underscores the need for genetic re-analysis in rare diseases. Further research is required to understand <i>CRB2</i>-related mechanisms.</p> Graphical abstract <p></p>

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Expanded CRB2-related disease phenotype: multisystem involvement and post-transplant complications in monozygotic twins

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月3日

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  • Moran Plonsky Toder,
  • Shirley Pollack,
  • Rami Tibi,
  • Irina Libinson-Zebegret,
  • Renata Yakubov,
  • Israel Eisenstein,
  • Mika Shapira Rootman,
  • Daniella Magen

摘要

Background

Congenital nephrotic syndrome (CNS) is a rare disorder caused by mutations in genes essential for podocyte function and glomerular slit diaphragm integrity, including CRB2 (Crumbs Cell Polarity Complex Component 2). CRB2 mutations are linked to focal segmental glomerulosclerosis and ventriculomegaly with cystic kidney disease, but their full phenotypic spectrum remains unclear. We describe the clinical course of monozygotic twins with a homozygous CRB2 mutation, highlighting severe complications following kidney transplantation.

Methods

The twins, who were followed and managed throughout their clinical course, were diagnosed with CNS after prenatal suspicion of polycystic kidney disease. Initial exome sequencing was negative, but subsequent whole exome sequencing revealed a homozygous CRB2 variant.

Results

Both twins presented with CNS, requiring intensive supportive care. Additional findings included cerebral heterotopia, cardiac involvement, and developmental delay. They both progressed to kidney failure, necessitating hemodialysis in early childhood. Post-transplant, the first twin succumbed to a systemic fungal infection, while the second developed complications linked to immune dysregulation, including post-transplant lymphoproliferative disease (PTLD), immune thrombocytopenic purpura (ITP), multiple viremias, and de novo donor-specific antibodies (DSA).

Conclusions

This case expands the phenotypic spectrum of CRB2-related disease, highlights management challenges, and underscores the need for genetic re-analysis in rare diseases. Further research is required to understand CRB2-related mechanisms.

Graphical abstract