In contrast with four cases of SLS recently reported in very young patients, the NPH1 gene (the main gene responsible for nephronophthisis) was not deleted in our two tested patients.
Because the disease is caused by large homozygous deletions of the NPHP1 gene in approximately 66% of patients with nephronophthisis, molecular genetic testing offers a method for the definite diagnosis of NPH1 and avoids the invasive procedure of renal biopsy.
Patients with clinical diagnosis of NPHP (n = 57) were screened for total deletion of NPHP1 by polymerase chain reaction (PCR) for the 20 exons of NPHP1.
Loci associated with an infantile type of NPHP on 9q22-q31 (NPHP2), juvenile types of NPHP on chromosomes 2q12-q13 (NPHP1) and 1p36 (NPHP4) and an adolescent type of NPHP on 3q21-q22 (NPHP3) have been mapped.
Also, we report that homozygous NPHP1 deletions account for 29.4% of NPHP in the studied families in this cohort, thereby confirming the diagnosis of type-1 NPHP.
Awareness of the histopathologic pattern of injury in nephronophthisis combined with testing for NPHP1 deletion enables renal pathologists to provide a definitive pathologic and genetic diagnosis in a subset of patients with this disease.
Homozygous deletions in the nephronophthisis 1 (NPHP1) gene are the major contributor of nephronophthisis cases, while other genes accounts for less than 3% each.
A control subject with NPHP and with a homozygous NPHP1 deletion was also identified, retrospectively, as having a mild MTS and borderline intelligence.
First, Inversin, a protein mutated in nephronophthisis type II was found to act as a switch between the canonical and the noncanonical Wnt cascade, suggesting that beta-catenin/TCF-dependent gene transcription has to be curtailed to allow normal tubular differentiation.
Mutational analysis of the two who survived beyond post-delivery demonstrated compound heterozygous novel frameshift mutations in the nephronophthisis type 3 gene (NPHP3).
Twenty-five percent of nephronophthisis cases are caused by large homozygous deletions of NPHP1, but six genes responsible for nephronophthisis have been identified.
To identify disease-causing mutations within coding regions of 11 known NPHP genes (NPHP1-NPHP11) in a cohort of 192 patients diagnosed with a nephronophthisis-associated ciliopathy, at low cost.
We recently reported hypomorphic NPHP3 mutations in children and young adults with isolated nephronophthisis and associated hepatic fibrosis or tapetoretinal degeneration.
The DNA sequence analysis of the polymerase chain reaction (PCR) detected no mutations in the NPHP2 (INVS) gene in this child, suggesting that new mutant genes might be responsible for the early onset of ESRD in infantile NPHP with features of JBTS.