Identification of a new locus for medullary cystic disease, on chromosome 16p12.

Autosomal dominant medullary cystic disease (ADMCKD) is an interstitial nephropathy that has morphologic and clinical features similar to autosomal recessive nephronophthisis. The typical renal dysfunction associated with ADMCKD results mainly from a defect in urinary concentration ability, although results of urinalysis are normal. Recently, a locus on chromosome 1 was associated with ADMCKD, in DNA from two large Cypriot families, and genetic heterogeneity was inferred. We describe the genomewide linkage mapping of a new locus for medullary cystic disease, ADMCKD2, on chromosome 16p12 in a four-generation Italian pedigree. The family with ADMCKD2 fulfills the typical diagnostic criteria of ADMCKD, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 shows a maximum two-point LOD score of 3.68, and the defined critical region spans 10.5 cM, between D16S500 and SCNN1B1-2. Candidate genes included in the critical region are discussed.     

Reaction of human serum albumin with aldoses

The reaction of human serum albumin (HSA) with aldoses (C3-C6) and acetaldehyde has been studied. U.v. and fluorescent spectra of the HSA-glyceraldehyde and HSA-GlcN adducts reveal yellow chromophores absorbing at 300-350 nm and emitting at 435 nm. However, even limited reaction of HSA with acetaldehyde induced perturbation in the Trp microenvironment. C.d. spectra of the adducts show an average 20% decrement in mean residual ellipticity [theta], which is independent of the extent of the reaction and the aldose used. It is concluded that most of the reactions with aldoses occur at the surface of the HSA molecule. With the exception of the GlcN adduct, the HSA adducts rearrange to produce pyrrole rings on the protein surface. I.e.f. analysis shows that the pI values of the modified HSA are almost linearly correlated with the chain length of the reacting aldose: from pI 4.2 for HSA-glyceraldehyde up to pI 5.0 for HSA-GlcN.