Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3Mb in a patient with Wolf-Hirschhorn syndrome
Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3Mb in a patient with Wolf-Hirschhorn syndrome
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DOI：
10.1038/sj.ejhg.5201899
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发表时间：
2007-11-01
影响因子：
5.2
通讯作者：
Poot, Martin
中科院分区：
文献类型：
--
作者：
Berg, Klara Flipsen-ten;Van Hasselt, Peter M.;Poot, Martin
The Wolf-Hirschhorn syndrome (WHS (MIM 194190)), which is characterized by growth delay, mental retardation, epilepsy, facial dysmorphisms, and midline fusion defects, shows extensive phenotypic variability. Several of the proposed mutational and epigenetic mechanisms in this and other chromosomal deletion syndromes fail to explain the observed phenotypic variability. To explain the complex phenotype of a patient with WHS and features reminiscent of Wolfram syndrome (WFS (MIM 222300)), we performed extensive clinical evaluation and classical and molecular cytogenetic (GTG banding, FISH and array-CGH) and WFS1 gene mutation analyses. We detected an 8.3Mb terminal deletion and an adjacent 2.6Mb inverted duplication in the short arm of chromosome 4, which encompasses a gene associated with WFS (WFS1). In addition, a nonsense mutation in exon 8 of the WFS1 gene was found on the structurally normal chromosome 4. The combination of the 4p deletion with the WFS1 point mutation explains the complex phenotype presented by our patient. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletions represents an additional explanation for the phenotypic variability observed in chromosomal deletion disorders.
