Molecular Diagnostics of ADPKD Coming of Age

Ever since the first autosomal dominant polycystic kidney disease (ADPKD) gene was localized to a chromosomal interval ( PKD1 : 16p13.3) in 1985, brave souls have been performing molecular-based diagnostics (1). The enthusiasm was tempered by the discovery of a second gene ( PKD2 : 4q21) and suggestions of a third, with the realization that reliable linkage-based diagnostics required families large enough to determine unequivocally the gene involved (2). Identification of the PKD1 and PKD2 genes in the mid 1990s revived interest, although the large coding region of PKD1 (approximately 13 kb) and reiteration of the genomic region several times elsewhere on chromosome 16 greatly complicated mutation screening (3,4). Consequently, the initial focus was mutations to the single-copy, 3′ region (approximately 20%) of PKD1 , and PKD2 (5,6). It was not until the dawning of the new millennium, after the development of methods for locus-specific amplification of the duplicated part of PKD1 , that comprehensive analysis of both genes was possible (7,8). Even then, indirect methods were used to screen for bp changes—methods that because of the level of precision were not …