Phenotype Spectrum in Tunisian Population with NPHP1 Deletion

Area of Science:

• Nephrology
• Genetics
• Pediatric Nephrology

Background:

• Nephronophthisis (NPHP) is an autosomal recessive tubulointerstitial kidney disease.
• Genetic heterogeneity of NPHP contributes to varied clinical presentations.
• Mutations in the NPHP1 gene are the most common cause of juvenile NPHP.

Purpose of the Study:

• To evaluate the genotype-phenotype correlation in NPHP1 gene mutations.
• To describe clinical, biological, and radiological features of NPHP1 large deletions.

Main Methods:

• A multicenter retrospective study.
• Involved 32 patients with NPHP1 large deletions.
• Data collected over 20 years (1998-2018).

Main Results:

• Incidence of NPHP1 was 1.6/204041.
• 81% of patients were from consanguineous marriages.
• Mean age at diagnosis was 14 ± 7 years.
• Clinical forms included isolated (72%), syndromic (19%), and unclassified (9%) NPHP.
• Variability in syndrome diagnosis and age of CKD stage 5 onset.
• Juvenile, adolescent, and adult forms of CKD onset observed.
• Five-year renal transplant survival rate was 80%.

Conclusions:

• A broad clinical spectrum is associated with NPHP1 large deletions.
• No definitive genotype-phenotype correlation could be established due to this variability.