A locus for adolescent and adult onset familial focal segmental glomerulosclerosis on chromosome 1q25-31.
Focal segmental glomerulosclerosis is a nonspecific renal lesion observed both as a primary (idiopathic) entity and in a secondary form, typically in association with reduced functional renal mass. Familial forms have been observed and two loci for autosomal dominant FSGS have been mapped. This study shows that an adolescent/adult form of recessive FSGS maps to a locus on chromosome 1q25-31, which overlaps with a region previously identified as harboring a locus for an early childhood onset recessive form of nephrotic syndrome (SRN1). Evaluation of a large family demonstrated linkage with a maximum two-point lod score of 3.98 at D1S254 and D1S222. Lod score calculations support the conclusion of linkage in four of five additional families. Haplotype analysis suggests that this FSGS gene is located in a 19-cM region flanked by D1S416 and D1S413, of which 6 cM overlaps with SRN1, suggesting that these distinct clinical subsets of kidney disease may be allelic. These regions may also overlap with the syntenic region of the glomerulosclerosis susceptibility locus in the BUF/Mna rat. Because the presentation of FSGS may be subtle, inherited FSGS may be much more common than generally realized and grossly underestimated because of the absence of clear familial patterns. This result increases the suspicion that polymorphisms at this locus may contribute to sporadic FSGS.
Tsukaguchi
Hiroyasu
H
Renal Division and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Yager
Henry
H
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts.
Dawborn
John
J
Department of Nephrology, Austin and Repatriation Medical Centre, Heidelberg, Australia.
Jost
Luis
L
Division of Nephrology, Instituto Universitario CEMIC, Buenos Aires, Argentina.
Cohlmia
Jerry
J
University of Kansas School of Medicine, Wichita, Kansas.
Abreu
Patricia F
PF
Division of Nephrology, Department of Medicine, Universidade Federal de São Paulo, Brazil.
Pereira
Aparecido B
AB
Division of Nephrology, Department of Medicine, Universidade Federal de São Paulo, Brazil.
Pollak
Martin R
MR
Renal Division and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D002648:Child; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree