In vivo functional modeling in zebrafish embryos demonstrated that c.14G>T is a loss-of-function variant, and suppression of nphp1 in concert with each of the primary BBS loci found in our NPHP1-positive pedigrees exacerbated the severity of the phenotype.
Our studies confirm that a T615P mutation represents the most common mutation in the RPGRIP1L gene causing disease in about 8-10% of JS type B patients negative for NPHP1, NPHP6, or AHI1 mutations.
We screened a population of 68 Italian children (10 multiplex families, 47 sporadic cases) with a clinical and histopathologic picture of NPH and found a large homozygous deletion at 2q13 involving nephrocystin in 30 cases, and heterozygous deletion associated with new point mutations at exons 15 (Tyr518Ter) and 17 (Arg585Ter) of the gene in two other cases.
We screened a population of 68 Italian children (10 multiplex families, 47 sporadic cases) with a clinical and histopathologic picture of NPH and found a large homozygous deletion at 2q13 involving nephrocystin in 30 cases, and heterozygous deletion associated with new point mutations at exons 15 (Tyr518Ter) and 17 (Arg585Ter) of the gene in two other cases.