Document Detail

Discordant phenotype of two overlapping deletions involving the PAX3 gene in chromosome 2q35.
MedLine Citation:
PMID:  8103404     Owner:  NLM     Status:  MEDLINE    
Waardenburg syndrome (WS), the most common form of inherited congenital deafness, is a pleiotropic, autosomal dominant condition with variable penetrance and expressivity. 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.
N G Pasteris; B J Trask; S Sheldon; J L Gorski
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human molecular genetics     Volume:  2     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-10-04     Completed Date:  1993-10-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  953-9     Citation Subset:  IM    
Department of Human Genetics, University of Michigan Medical Center, Ann Arbor 48109-0688.
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MeSH Terms
Bone and Bones / abnormalities
Child, Preschool
Chromosome Deletion*
Chromosomes, Human, Pair 2*
Cleft Palate / genetics
Genes, Dominant
Genes, Homeobox*
Genetic Markers
In Situ Hybridization, Fluorescence
Mental Retardation / genetics
Microcephaly / genetics
Waardenburg's Syndrome / classification,  genetics*
Grant Support
Reg. No./Substance:
0/Genetic Markers

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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