Human PRRX1 and PRRX2 genes: cloning, expression, genomic localization, and exclusion as disease genes for Nager syndrome

Ln this study, we extend our examination of the function of the Prrx1 (a.k. a. Mhox, Prx1, K-2, and Pmx1) as well as Prrx2 (a.k.a. S8 and Prx2) genes b y characterizing the expression of the human orthologs and their potential for causing specific human malformations. The expression pattern of PRRX2 a nd its close relative, PRRX1, were analyzed in human tissue by RT-PCR. Alth ough the expression of these human genes is similar to their mouse ortholog s, there are notable differences in expression. PRRX2 was detected in the h uman kidney and lung, whereas in mice and chickens neither of these tissues has been reported to express Prrx2. For PRRX1 the expression pattern was q uite similar to other vertebrates, but the ratio of the two isoforms was re versed. To begin the search for the gene-disease connection, both genes wer e mapped to human chromosomes by FISH. The PRRX1 locus maps to 1q23, wherea s the PRRX2 locus maps to 9q34.1. This localization, along with the recentl y described phenotypes of the gene-targeted Prrx1, Prrx2 and double mutant mice, enabled us to search the human disease databases for similar malforma tions. This examination suggested that mutations at the PRRX1 and/or PRRX2 loci could result in Nager Acrofacial Dysostosis (NAFD) syndrome. We obtain ed DNA samples from eight patients with NAFD, as well as two patients with Miller syndrome, and analyzed them for mutations in the PRRX1 and PRRX2 gen es. The data excludes mutations in the presumed coding sequences of these g enes from causing NAFD.