caa a22 4500 397575955 CHVBK 20180308164856.0 cr unu---uuuuu 161202e199604 xx s 000 0 eng 10.1093/hmg/5.4.497 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.4.497 Phenotypic Variation in Waardenburg Syndrome: Mutational Heterogeneity, Modifier Genes or Polygenic Background? [Elektronische Daten] [Arti Pandya, Xia-Juan Xia, Barbara L. Landa, Kathleen S. Arnos, Jamie Israel, Joyce Lloyd, Anthony L. James, Scott R. Diehl, Susan H. Blanton, Walter E. Nance] We have identified 11 mutational changes in the PAX3 gene in patients with type 1 Waardenburg syndrome (WS1) including three in the paired domain, six within or immediately adjacent to the homeodomain and two previously described polymorphic variants in exons 2 and 6. The affected members of one family carried substitutions involving two base pairs separated by one unaltered codon. Two of the deleterious mutations were identical and three others were identical to previously reported mutations. A comparison of clinical findings in families carrying substitutions in the same codon failed to reveal conspicuous similarities. Although subtle mutation-specific effects may well exist, allelic heterogeneity clearly cannot account for within family variation. However, the striking concordance of a pair of monozygotic twins with Waardenburg syndrome (WS) and previous reports of similar pairs indicate that phenotypic variation in WS has a genetic basis. If the genetic effects are mediated by oligogenic epistasis, as studies in the mouse suggest, it may ultimately be possible to predict clinically relevant aspects of the Waardenburg phenotype. © 1996 Oxford University Press Pandya Arti Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut Xia Xia-Juan Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut Landa Barbara L. Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut Arnos Kathleen S. Gallaudet University, , Washington D.C. 20002USA aut Israel Jamie Gallaudet University, , Washington D.C. 20002USA aut Lloyd Joyce Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut James Anthony L. Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut Diehl Scott R. Molecular Epidemiology and Disease Indicators Branch, DEODP, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA aut Blanton Susan H. Department of Pediatrics, University of Virginia, Charlottesville, Virginia 22908, USA aut Nance Walter E. Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut Human Molecular Genetics Oxford University Press 5/4(1996-04), 497-502 0964-6906 5:4<497 1996 5 hmg https://doi.org/10.1093/hmg/5.4.497 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.4.497 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pandya Arti Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut NATIONALLICENCE 700 1- Xia Xia-Juan Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut NATIONALLICENCE 700 1- Landa Barbara L. Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut NATIONALLICENCE 700 1- Arnos Kathleen S. Gallaudet University, , Washington D.C. 20002USA aut NATIONALLICENCE 700 1- Israel Jamie Gallaudet University, , Washington D.C. 20002USA aut NATIONALLICENCE 700 1- Lloyd Joyce Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut NATIONALLICENCE 700 1- James Anthony L. Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut NATIONALLICENCE 700 1- Diehl Scott R. Molecular Epidemiology and Disease Indicators Branch, DEODP, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA aut NATIONALLICENCE 700 1- Blanton Susan H. Department of Pediatrics, University of Virginia, Charlottesville, Virginia 22908, USA aut NATIONALLICENCE 700 1- Nance Walter E. Department of Human Genetics, Medical College of Virginia, Richmond, VA 23298, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/4(1996-04), 497-502 0964-6906 5:4<497 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford