Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria.

Abstract

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 re-sequencing. 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.

• Authors: Bugsu Ovunc, Edgar A Otto, Virginia Vega-Warner, Pawaree Saisawat, Shazia Ashraf, Gokul Ramaswami, Hanan M Fathy, Dominik Schoeb, Gil Chernin, Robert H Lyons, Engin Yilmaz, Friedhelm Hildebrandt
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 22 Issue 10 Pg. 1815-20 (Oct 2011) ISSN: 1533-3450 [Electronic] United States
• PMID: 21903995 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Cell Surface
• intrinsic factor-cobalamin receptor

Topics

• Exome
• Frameshift Mutation
• Genes, Recessive
• Homozygote
• Humans
• Proteinuria (genetics)
• Receptors, Cell Surface (genetics)