© 1993 Oxford University Press
RESEARCH-ARTICLE |
Discordant phenotype of two overlapping deletions involving the PAX3 gene in chromosome 2q35
1Departments of Human Genetics, University of Michigan Medical Center Ann Arbor, MI 48109–0688 2Departments of Pathotogy, University of Michigan Medical Center Ann Arbor, MI 48109–0688 3Departments of Pediatncs and Communicable Diseases, University of Michigan Medical Center Ann Arbor, MI 48109–0688 4Human Genome Center, Lawrence Livermore National Laboratory Livermore, CA 94550, USA
* To whom correspondence should be addressed at: Division of Pediatric Genetics, 3570 Medical Science Research Building II, Box 0688, University of Michigan Medical Center, Ann Arbor, MI 48109-0688, USA
Received March 9, 1993; Revised April 21, 1993; Accepted April 21, 1993
Waardenburg syndrome (WS), the most common form of Inherited congenltal deafness, is a pleiotropic, autosomal dominant condition with variable penetrance and expresslvity. WS is clinically and genetically heterogeneous. The basis for the phenotypic variability observed among and between WS families is unknown. However, mutations within the paired-box gene, PAX3, have been associated with a subset of WS patients. In this report we use cytogenetic and molecular genetic techniques to study a patient with WS type 3, a form of WS consisting of typical WS type 1 features plus mental retardation, microcephaly, and severe skeletal anomalies. Our results show that the WS3 patient has a de novo paternally derived deletion, del (2)(q35q36), that spans the genetic loci PAX3 and COL4A3. A molecular analysis of a chromosome 2 deletional mapping panel maps the PAX3 locus to 2q35 and suggests the locus order: centromere-(INHA, DES)-PAX3-COL4A3-(ALPI, CHRND)-telomere. Our analyses also show that a patient with a cleft palate and lip pits, but lacking diagnostic WS features, has a deletion, del (2)(q33q35), Involving the PAX3 locus. This result suggests that not all PAX3 mutations are associated with a WS phenotype and that additional regional loci may modify or regulate the PAX3 locus and/or the development of a WS phenotype.
+ Present adress: Department of Molecular Boitechnology, University of Washington School of Medicine, Gj10, Seattle, WA 98195, USA
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  I Borg, M Squire, C Menzel, K Stout, D Morgan, L Willatt, P C M O'Brien, M A Ferguson-Smith, H H Ropers, N Tommerup, et al. A cryptic deletion of 2q35 including part of the PAX3 gene detected by breakpoint mapping in a child with autism and a de novo 2;8 translocation J. Med. Genet., June 1, 2002; 39(6): 391 - 399. [Abstract] [Full Text] [PDF]
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