title: 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: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Bugsu
authors: B
authors: Ovunc
authors: Edgar A
authors: EA
authors: Otto
authors: Virginia
authors: V
authors: Vega-Warner
authors: Pawaree
authors: P
authors: Saisawat
authors: Shazia
authors: S
authors: Ashraf
authors: Gokul
authors: G
authors: Ramaswami
authors: Hanan M
authors: HM
authors: Fathy
authors: Dominik
authors: D
authors: Schoeb
authors: Gil
authors: G
authors: Chernin
authors: Robert H
authors: RH
authors: Lyons
authors: Engin
authors: E
authors: Yilmaz
authors: Friedhelm
authors: F
authors: Hildebrandt
mesh_terms: D059472:Exome; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D011507:Proteinuria / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor