Identification of the human CYS1 gene and candidate gene analysis in Boichis disease.

Recessive mutations cause cystic kidney disease and a variable degree of biliary liver fibrosis in cpk mice. Recently, the responsible murine gene ( Cys1) was identified and expression in renal cilia demonstrated. Here we describe the cDNA cloning of the full-length coding region of the orthologous human CYS1 gene. CYS1 is located on Chromosome 2p25. The CYS1 genomic region comprises three coding exons, which span 22 kb. The transcript harbors an open reading frame of 477 nucleotides encoding a protein with 158 amino acid residues, which is called cystin. Northern analysis identified an expression pattern resembling that of murine Cys1. We studied affected individuals of eight families with nephronophthisis and liver fibrosis for evidence of CYS1 mutations. All three coding exons were amplified by polymerase chain reaction and directly sequenced. Despite the failure to detect a mutation, the human cystin gene remains an interesting candidate for recessive cystic kidney disease.