Publication
Title
PORCN Mutations in Focal Dermal Hypoplasia: Coping with Lethality
Author
Abstract
The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23. Three were microdeletions eliminating PORCN and encompassing neighboring genes such as EBP, the gene associated with Conradi-Hunermann-Happle syndrome (CDPX2). 12/24 patients carried nonsense mutations resulting in loss of function. In one case a canonical splice acceptor site was mutated, and 8 missense mutations exchanged highly conserved amino acids. FDH patients overcome the consequences of potentially lethal X-chromosomal mutations by extreme skewing of X-chromosome inactivation in females, enabling transmission of the trait in families, or by postzygotic mosaicism both in male and female individuals. Molecular characterization of the PORCN mutations in cases diagnosed as Goltz syndrome is particularly relevant for genetic counseling of patients and their families since no functional diagnostic test is available and carriers of the mutation might otherwise be overlooked due to considerable phenotypic variability associated with the mosaic status. c 2009 Wiley-Liss, Inc.
Language
English
Source (journal)
Human mutation. - New York, N.Y.
Publication
New York, N.Y. : 2009
ISSN
1059-7794
Volume/pages
30 :5 (2009) , p. E618-E628
ISI
000279669100003
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.11.2018
Last edited 06.11.2021