LACK OF LARGE, HOMOZYGOUS DELETIONS OF THE NEPHRONOPHTHISIS-1 REGION IN JOUBERT-SYNDROME TYPE-B

Joubert syndrome type B (JSB) is a developmental disorder of the nephr onophthisis (NPH) complex with multiple organ involvement, including N PH, coloboma of the eye, aplasia of the cerebellar vermis, and the fac ultative symptoms of psychomotor retardation, polydactyly, and neonata l tachypnea. In isolated autosomal recessive NPH type 1 (NPH1), homozy gous deletions have been described as causative in more than 80% of pa tients. Since different combinations of the extrarenal symptoms with N PH occur in JSB, a contiguous gene deletion syndrome in the NPH1 genet ic region would seem a highly likely cause for JSB. We therefore exami ned 11 families with JSB for the presence of extended deletions at the NPH1 locus. Genomic DNA was examined using four consecutive polymeras e chain reaction (PCR) markers that are deleted in NPH1 and three PCR makers flanking the NPH1 deletion. In all seven markers examined, ther e was no homozygous deletion detected in any of the 11 JSB families st udied. Since these markers saturate the NPH1 deletion region at high d ensity, this finding excludes the presence of large homozygous deletio ns of the NPH1 region in these JSB families, making it unlikely that d eletions of the NPH1 region are a primary cause for JSB.