A BEDOUIN KINDRED WITH INFANTILE NEPHRONOPHTHISIS DEMONSTRATES LINKAGE TO CHROMOSOME 9 BY HOMOZYGOSITY MAPPING

A novel type of infantile nephronophthisis was identified in an extend ed Bedouin family from Israel. This disease has an autosomal recessive mode of inheritance, with the phenotypic presentation ranging from a Potter-like syndrome to hyperechogenic kidneys, renal insufficiency, h ypertension, and hyperkalemia, Affected individuals show rapid deterio ration of kidney function, leading to end-stage renal failure within 3 years. Histopathologic examination of renal tissue revealed variable findings, ranging from infantile polycystic kidneys to chronic tubuloi nterstitial nephritis, fibrosis, and cortical microcysts, A known fami lial juvenile nepbronophthisis locus on chromosome 2q13 and autosomal recessive polycystic kidney disease on chromosome 6p21.1-p1.2 were exc luded by genetic linkage analysis. A genomewide screen for linkage was conducted by searching for a locus inherited by descent in all affect ed individuals. Pooled DNA samples from parents and unaffected sibling s and individual DNA samples from four affected individuals were used as PCR templates with trinucleotide- and tetranucleotide-repeat polymo rphic markers. Using this approach, we identified linkage to infantile nephronophthisis for markers on chromosome 9q22-31. The disorder maps to a 12.8-cM region flanked by markers D9S280 and GGAT3C09.