Three loci had been mapped for nephronophthisis, the leading genetic cause of chronic renal failure in young adults: juvenile NPHP1 (256100) on 2q13; infantile nephronophthisis (NPHP2; 602088) on 9q22-q31; and adolescent nephronophthisis (NPHP3; 604387) on 3q21-q22. By renal ... Three loci had been mapped for nephronophthisis, the leading genetic cause of chronic renal failure in young adults: juvenile NPHP1 (256100) on 2q13; infantile nephronophthisis (NPHP2; 602088) on 9q22-q31; and adolescent nephronophthisis (NPHP3; 604387) on 3q21-q22. By renal histology the 3 forms of the disease are indistinguishable, all 3 exhibiting a triad of interstitial-cell infiltrates, renal tubular-cell atrophy with cysts arising from the corticomedullary junction of the kidneys, and renal interstitial fibrosis (Waldherr et al., 1982). Clinically, there is a statistically different age at onset at end-stage renal disease: terminal renal failure develops at median ages of 1 year, 13 years, and 19 years, in NPHP2, NPHP1, and NPHP3, respectively (Omran et al., 2000). In the patients studied by Schuermann et al. (2002), who reported the chromosomal localization of a fourth gene locus, NPHP4, end-stage renal disease commenced within a wide age range, 11 to 34 years.
To narrow the location of the NPHP4 gene, Mollet et al. (2002) carried out haplotype analysis of families with nephronophthisis that did not show linkage to NPHP1, NPHP2, or NPHP3, using markers covering the 1p36 region. This allowed ... To narrow the location of the NPHP4 gene, Mollet et al. (2002) carried out haplotype analysis of families with nephronophthisis that did not show linkage to NPHP1, NPHP2, or NPHP3, using markers covering the 1p36 region. This allowed them localize the NPHP4 gene within a 1-cM interval between D1S2795 and D1S2870, which contained 6 genes. They identified 5 mutations in 1 of these genes, designated NPHP4, in unrelated individuals with nephronophthisis; see 607215.0001-607215.0005.