Characterization of a novel gene, PNUTL2, on human chromosome 17q22-q23 and its exclusion as the Meckel syndrome gene.

We assigned two human expressed sequence tags (ESTs), WI-15444 and SGC32067, homologous to mouse brain protein h5, to the critical region for Meckel syndrome (MKS) on 17q22-q23. For the sequence analyses in MKS patients, we isolated the corresponding human gene, PNUTL2, by analyzing an Image cDNA clone that contained these ESTs. Based on sequence homologies, the gene belongs to an expanding family of GTP-binding proteins, septins, that are involved in cytokinesis. In Northern analysis, PNUTL2 is ubiquitously expressed as a 1.7-kb transcript in adult and fetal tissues with particularly high expression in the heart, liver, and adrenal gland. Mutation analysis using sequencing of RT-PCR products and Northern blot analysis in MKS patients exclude PNUTL2 as the gene for MKS.