ABSTRACT
In 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 by characterizing the expression of the human orthologs and their potential for causing specific human malformations. The expression pattern of PRRX2 and its close relative, PRRX1, were analyzed in human tissue by RT-PCR. Although the expression of these human genes is similar to their mouse orthologs, there are notable differences in expression. PRRX2 was detected in the human kidney and lung, whereas in mice and chickens neither of these tissues has been reported to express Prrx2. For PRRX1 the expression pattern was quite similar to other vertebrates, but the ratio of the two isoforms was reversed. To begin the search for the gene-disease connection, both genes were mapped to human chromosomes by FISH. The PRRX1 locus maps to 1q23, whereas the PRRX2 locus maps to 9q34.1. This localization, along with the recently described phenotypes of the gene-targeted Prrx1, Prrx2 and double mutant mice, enabled us to search the human disease databases for similar malformations. This examination suggested that mutations at the PRRX1 and/or PRRX2 loci could result in Nager Acrofacial Dysostosis (NAFD) syndrome. We obtained 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 genes. The data excludes mutations in the presumed coding sequences of these genes from causing NAFD.
Subject(s)
Abnormalities, Multiple/genetics , Homeodomain Proteins/genetics , Mandibulofacial Dysostosis/genetics , Alleles , Amino Acid Sequence , Animals , Chromosome Mapping , Chromosomes, Human, Pair 9 , Cloning, Molecular , Gene Expression Regulation, Developmental , Humans , Mice , Miller Fisher Syndrome/genetics , Molecular Sequence Data , Mutation , Sequence Homology, Amino Acid , SyndromeABSTRACT
Children with phonology disorders frequently show reduced performance in short-term recall, inviting the assumption that impairment of memory may cause or help to cause the speech disorder. Ten children with marked phonology disorders were compared to 10 correctly speaking children on a test of short-term memory for sets of pictures whose names rhymed or did not rhyme. The phonologically disordered children performed significantly worse than those with correct speech and provided less evidence of phonetic mediation, a process commonly associated with enhanced levels of recall. Attention is drawn to the possibility that the disorder of phonology operated indirectly to reduce the efficiency of memory, though the question is complicated.