Exome Sequencing Reveals Cubilin Mutation as a Single-Gene Cause of Proteinuria


Ovunc B., Otto E. A. , Vega-Warner V., Saisawat P., Ashraf S., Ramaswami G., ...Daha Fazla

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, cilt.22, sa.10, ss.1815-1820, 2011 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Konu: 10
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1681/asn.2011040337
  • Dergi Adı: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
  • Sayfa Sayıları: ss.1815-1820

Özet

In two siblings of consanguineous parents with intermittent nephrotic-range proteinuria, we identified a homozygous deleterious frameshift mutation in the gene CUBN, which encodes cubulin, using exome capture and massively parallel resequencing. The mutation segregated with affected members of this family and was absent from 92 healthy individuals, thereby identifying a recessive mutation in CUBN as the single-gene cause of proteinuria in this sibship. Cubulin mutations cause a hereditary form of megaloblastic anemia secondary to vitamin B-12 deficiency, and proteinuria occurs in 50% of cases since cubilin is coreceptor for both the intestinal vitamin B-12-intrinsic factor complex and the tubular reabsorption of protein in the proximal tubule. In summary, we report successful use of exome capture and massively parallel re-sequencing to identify a rare, single-gene cause of nephropathy.