Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf–Hirschhorn syndrome
| Autor: | Klara Flipsen-ten Berg, P F Ron Hochstenbach, Martin Poot, Marc J. Eleveld, Frits A. Beemer, Peter M. van Hasselt, Suzanne E van der Wijst, Monique A. M. J. de Vroede, Frans A. Hol |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Heterozygote Nonsense mutation Biology medicine.disease_cause Genomic disorders and inherited multi-system disorders [IGMD 3] Gene mapping Genetics medicine Humans Point Mutation Deletion mapping Wolf–Hirschhorn syndrome Genetics (clinical) Chromosomal Deletion Molecular diagnosis prognosis and monitoring [UMCN 1.2] Mutation Wolf-Hirschhorn Syndrome Point mutation Homozygote Infant Newborn Infant Membrane Proteins medicine.disease Phenotype Chromosome 4 Codon Nonsense Child Preschool Female Chromosome Deletion Chromosomes Human Pair 4 |
| Zdroj: | European Journal of Human Genetics, 15, 11, pp. 1132-8 European Journal of Human Genetics, 15, 1132-8 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/sj.ejhg.5201899 |
| Popis: | Contains fulltext : 36655.pdf (Publisher’s version ) (Closed access) 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 8.3 Mb terminal deletion and an adjacent 2.6 Mb 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. |
| Databáze: | OpenAIRE |
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