Review of this disorder and related syndromes suggests that (1) hypoplasia of the cerebellar vermis in Joubert syndrome is frequently associated with a complex brain stem malformation represented as the "molar tooth sign" on magnetic resonance imaging, (2) the "molar tooth sign" could be present in association with the Dandy-Walker malformation and occipital encephalocele, (3) cerebellar hypoplasia is present in conditions related to Joubert syndrome such as Arima syndrome; Senior-Loken syndrome; cerebellar vermian hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis syndrome; and juvenile nephronophthisis due to NPH1 mutations, and (4) the brainstem-vermis malformation spectrum is probably caused by at least two and probably several genetic loci.
This contig assembly provides the basis for closer definition of the NPH1 critical region through identification of more narrow flanking markers and for the construction of a transcriptional map of the region towards isolation of the NPH1 gene.
A gene (NPH1) responsible for approximately 90% of the purely renal form of familial juvenile nephronophthisis, a progressive tubulo-interstitial kidney disorder, maps to human chromosome 2.