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Related Experiment Video

Updated: May 22, 2026

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NPHP4 variants are associated with pleiotropic heart malformations.

Vanessa M French¹, Ingrid M B H van de Laar, Marja W Wessels

¹Department of Clinical Genetics, Erasmus MC Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

Circulation Research

|May 3, 2012

Summary

Mutations in NPHP4 cause congenital heart defects and heterotaxy by disrupting left-right body patterning. NPHP4 is crucial for cilia function in zebrafish, essential for normal organ development.

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Area of Science:

Developmental Biology
Genetics
Human Physiology

Background:

Congenital heart malformations are a leading cause of childhood mortality.
Improper left-right (L-R) asymmetry establishment leads to cardiovascular and visceral defects.

Purpose of the Study:

To identify genetic causes of cardiac laterality defects.
Investigate the role of NPHP4 in L-R asymmetry.

Main Methods:

Genome-wide linkage analysis in a consanguineous family.
NPHP4 mutation analysis in 146 unrelated patients.
Zebrafish nphp4 knockdown and rescue experiments.

Main Results:

Identified NPHP4 mutations in patients with cardiac laterality defects.
NPHP4 variants were associated with heterotaxy in 41% of patients.
Zebrafish nphp4 depletion disrupted L-R patterning and cilia formation.

Conclusions:

NPHP4 mutations are linked to cardiac laterality defects and heterotaxy.
NPHP4 is essential for Kupffer's vesicle cilia function and L-R patterning in zebrafish.