title: IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23.
abstract: End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Gharavi
authors.forename: Y
authors.initials: Y
authors.lastname: Yan
authors.forename: F
authors.initials: F
authors.lastname: Scolari
authors.forename: F P
authors.initials: FP
authors.lastname: Schena
authors.forename: G M
authors.initials: GM
authors.lastname: Frasca
authors.forename: G M
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: K
authors.initials: K
authors.lastname: Cooper
authors.forename: A
authors.initials: A
authors.lastname: Amoroso
authors.forename: B F
authors.initials: BF
authors.lastname: Viola
authors.forename: G
authors.initials: G
authors.lastname: Battini
authors.forename: G
authors.initials: G
authors.lastname: Caridi
authors.forename: C
authors.initials: C
authors.lastname: Canova
authors.forename: A
authors.initials: A
authors.lastname: Farhi
authors.forename: V
authors.initials: V
authors.lastname: Subramanian
authors.forename: C
authors.initials: C
authors.lastname: Nelson-Williams
authors.forename: S
authors.initials: S
authors.lastname: Woodford
authors.forename: B A
authors.initials: BA
authors.lastname: Julian
authors.forename: R J
authors.initials: RJ
authors.lastname: Wyatt
authors.forename: R P
authors.initials: RP
authors.lastname: Lifton
mesh_terms: D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D010375:Pedigree; D014481:United States