Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome

Simone Sanna-Cherchi*, Katelyn Elizabeth Burgess, Shannon N. Nees, Gianluca Caridi, Patricia L. Weng, Monica Dagnino, Monica Bodria, Alba Carrea, Maddalena A. Allegretta, Hyunjae R. Kim, Brittany J. Perry, Maddalena Gigante, Lorraine N. Clark, Sergey Kisselev, Daniele Cusi, Loreto Gesualdo, Landino Allegri, Francesco Scolari, Vivette D'Agati, Lawrence S. ShapiroCarmine Pecoraro, Teresa Palomero, Gian M. Ghiggeri, Ali G. Gharavi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


To identify gene loci associated with steroid-resistant nephrotic syndrome (SRNS), we utilized homozygosity mapping and exome sequencing in a consanguineous pedigree with three affected siblings. High-density genotyping identified three segments of homozygosity spanning 33.6 Mb on chromosomes 5, 10, and 15 containing 296 candidate genes. Exome sequencing identified two homozygous missense variants within the chromosome 15 segment; an A159P substitution in myosin 1E (MYO1E), encoding a podocyte cytoskeletal protein; and an E181K substitution in nei endonuclease VIII-like 1 (NEIL1), encoding a base-excision DNA repair enzyme. Both variants disrupt highly conserved protein sequences and were absent in public databases, 247 healthy controls, and 286 patients with nephrotic syndrome. The MYO1E A159P variant is noteworthy, as it is expected to impair ligand binding and actin interaction in the MYO1E motor domain. The predicted loss of function is consistent with the previous demonstration that Myo1e inactivation produces nephrotic syndrome in mice. Screening 71 additional patients with SRNS, however, did not identify independent NEIL1 or MYO1E mutations, suggesting larger sequencing efforts are needed to uncover which mutation is responsible for the phenotype. Our findings demonstrate the utility of exome sequencing for rapidly identifying candidate genes for human SRNS.

Original languageEnglish (US)
Pages (from-to)389-396
Number of pages8
JournalKidney international
Issue number4
StatePublished - Aug 2 2011


  • homozygosity mapping
  • nephrotic syndrome
  • next-generation sequencing

ASJC Scopus subject areas

  • Nephrology


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