Molecular Genetic Studies of Tunisian Patients with Juvenile Nephronophtisis

Juvenile nephronophtisis (NPHP), a rare recessive cystic kidney disease, represents the most common genetic cause of endstage renal disease in the first two decades of life. A few studies have investigated the clinical and molecular characteristics of NPHP and related ciliopathies in the Tunisian population. We reported the results of the largest molecular genetic investigation. Since 2004, 71 patients were recruited, 33 children and 38 adult, with a median age of 11 and 32.7±6.1 years and belongs to 27 and 34 unrelated families respectively. Mutations causing NPHP were detected in 10 index cases (14%), belongs to nine independent families. Eight of them (7 Children, one adult) were homozygous for the NPHP1 gene deletion. For the two others, we detected two NPHP4 mutations in homozygous state: a novel missense mutation His1363Pro and a deletion of exons 2 and 3. After relatives investigations the final number increases to 29 patients, 18 carrying NPHP1 deletion and 11 with NPHP4 mutations. Extra-renal abnormalities were present in 27.5% of patients, including retinitis pigmentosa, neurological defects or hearing loss. This detection of the NPHP variations have important implications for genetic counseling towards the identification and care of asymptomatic siblings, then planning of renal replacement therapy.