Duplication of theZIC2Gene is not Associated With Holoprosencephaly

    loading  Checking for direct PDF access through Ovid


Cytogenetic testing using genomic microarrays presents a clinical challenge when data regarding the phenotypic consequences of the genomic alteration are not available. We describe a chromosome 13q32.3 duplication discovered by microarray testing in a fetus with a prenatally detected apparently balanced de novo translocation 46,XY,t(2;13)(q37;q32). Microarray analysis on the fetal DNA showed duplications of 384 and 564 kb at the breakpoint regions on chromosomes 2q37.3 and 13q32.3, respectively. There were no disease–associated genes in the duplicated region on chromosome 2q37. The duplicated region on chromosome 13q contains theZIC2gene. Haploinsufficiency ofZIC2is known to cause holoprosencephaly and other brain malformations. Studies in the mouse models have suggested that over expression ofZIC2may also lead to brain malformations. Fetal MRI of the brain was normal and the family elected to continue the pregnancy. An apparently normal baby was born at term. At 3 months of age a physical exam showed no abnormalities and no developmental delay. This report shows that duplication ofZIC2is not necessarily associated with brain malformations. We also describe the phenotype from four additional patients with duplications of the region of chromosome 13 containingZIC2and three previously described patients with supernumerary marker chromosomes derived from distal chromosome 13. None of the eight patients had holoprosencephaly or brain malformations, indicating that duplication ofZIC2is not associated with brain anomalies. This information will be useful for counseling in other occurrences of this duplication identified by microarray. © 2011 Wiley Periodicals, Inc.

Related Topics

    loading  Loading Related Articles