A locus for adolescent and adult onset familial focal segmental glomerulosclerosis on chromosome 1q25-31

Focal segmental glomerulosclerosis is a nonspecific renal lesion observed b oth as a primary (idiopathic) entity and in a secondary form, typically in association with reduced functional renal mass. Familial forms have been ob served and two loci for autosomal dominant FSGS have been mapped. This stud y 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 h arboring a locus for an early childhood onset recessive form of nephrotic s yndrome (SRN1). Evaluation of a large family demonstrated linkage with a ma ximum two-point lod score of 3.98 at D1S254 and D1S222. Lod score calculati ons support the conclusion of linkage in four of five additional families. Haplotype analysis suggests that this FSGS gene is located in a 19-cM regio n flanked by D1S416 and D1S413, of which 6 cM overlaps with SRN1, suggestin g that these distinct clinical subsets of kidney disease may be allelic. Th ese regions may also overlap with the syntenic region of the glomeruloscler osis susceptibility locus in the BUF/Mna rat. Because the presentation of F SGS may be subtle, inherited FSGS may be much more common than generally re alized and grossly underestimated because of the absence of clear familial patterns. This result increases the suspicion that polymorphisms at this lo cus may contribute to sporadic FSGS.