Mammalian Genome

, Volume 11, Issue 11, pp 1000-1005

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

  • Russell A.  NorrisAffiliated withMedical University of South Carolina, Department of Cell Biology and Anatomy, 171 Ashley Ave., Charleston, South Carolina 29425-2204, USA
  • , Karen K.  ScottAffiliated withMedical University of South Carolina, Department of Cell Biology and Anatomy, 171 Ashley Ave., Charleston, South Carolina 29425-2204, USA
  • , Clara S.  MooreAffiliated withJohns Hopkins University School of Medicine, Department of Gynecology and Obstetrics, 600 N. Wolfe Street, Baltimore, Maryland 21287-2501, USA
  • , Gail  StettenAffiliated withJohns Hopkins University School of Medicine, Department of Gynecology and Obstetrics, 600 N. Wolfe Street, Baltimore, Maryland 21287-2501, USA
  • , Cuyler R.  BrownAffiliated withMedical University of South Carolina, Department of Cell Biology and Anatomy, 171 Ashley Ave., Charleston, South Carolina 29425-2204, USA
  • , Ethylin Wang  JabsAffiliated withJohns Hopkins University School of Medicine, Center for Craniofacial Development and Disorders, Institute of Genetic Medicine, Departments of Pediatrics, Medicine, and Surgery, 600 N. Wolfe Street, Baltimore, Maryland 21287-3914, USA
  • , Eric A.  WulfsbergAffiliated withUniversity of Maryland at Baltimore, Division of Human Genetics, 22 S. Greene Street, N6E10, Baltimore, Maryland 21201, USA
  • , Jack  YuAffiliated withMedical College of Georgia, Department of Surgery, 1467 Harper Street HB-5040, Augusta, Georgia 30912, USA
  • , Michael J.  KernAffiliated withMedical University of South Carolina, Department of Cell Biology and Anatomy, 171 Ashley Ave., Charleston, South Carolina 29425-2204, USA

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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.