LARGE HOMOZYGOUS DELETIONS OF THE 2Q13 REGION ARE A MAJOR CAUSE OF JUVENILE NEPHRONOPHTHISIS

Juvenile nephronophthisis (NPH) is a genetically heterogeneous disorde r representing the most frequent inherited cause of chronic renal fail ure in children, We recently assigned a gene (NPH1) to the 2q13 region which is responsible for approximately 85% of cases, Cloning this reg ion in a yeast artificial chromosome contig revealed the presence of l ow copy repeats, Large-scale rearrangements were detected in 80% of th e patients belonging to inbred or multiplex NPH1 families and in 65% o f the sporadic cases, Surprisingly, these rearrangements seem to be, i n most cases, large homozygous deletions of approximately 250 kb invol ving an 100 kb inverted duplication, This suggests a common genetic di sease-causing mechanism, which could be responsible for the highest fr equency of large rearrangements reported in an autosomal recessive tra it, Our findings are also of major clinical interest, as they permit t he diagnosis in the majority of sporadic cases without the need for ki dney biopsy.