Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

Mutations in ZIC2 in human holoprosencephaly: description of a Novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals JOURNAL OF MEDICAL GENETICS Solomon, B. D., Lacbawan, F., Mercier, S., Clegg, N. J., Delgado, M. R., Rosenbaum, K., Dubourg, C., David, V., Olney, A. H., Wehner, L., Hehr, U., Bale, S., Paulussen, A., Smeets, H. J., Hardisty, E., Tylki-Szymanska, A., Pronicka, E., Clemens, M., McPherson, E., Hennekam, R. C., Hahn, J., Stashinko, E., Levey, E., Wieczorek, D., Roeder, E., Schell-Apacik, C. C., Booth, C. W., Thomas, R. L., Kenwrick, S., Cummings, D. A., Bous, S. M., Keaton, A., Balog, J. Z., Hadley, D., Zhou, N., Long, R., Velez, J. I., Pineda-Alvarez, D. E., Odent, S., Roessler, E., Muenke, M. 2010; 47 (8): 513-524

Abstract

Holoprosencephaly (HPE), the most common malformation of the human forebrain, may be due to mutations in genes associated with non-syndromic HPE. Mutations in ZIC2, located on chromosome 13q32, are a common cause of non-syndromic, non-chromosomal HPE.To characterise genetic and clinical findings in patients with ZIC2 mutations.Through the National Institutes of Health and collaborating centres, DNA from approximately 1200 individuals with HPE spectrum disorders was analysed for sequence variations in ZIC2. Clinical details were examined and all other known cases of mutations in ZIC2 were included through a literature search.By direct sequencing of DNA samples of an unselected group of unrelated patients with HPE in our NIH laboratory, ZIC2 mutations were found in 8.4% (49/582) of probands. A total of 157 individuals from 119 unrelated kindreds are described, including 141 patients with intragenic sequence determined mutations in ZIC2. Only 39/157 patients have previously been clinically described. Unlike HPE due to mutations in other genes, most mutations occur de novo and the distribution of HPE types differs significantly from that of non-ZIC2 related HPE. Evidence is presented for the presence of a novel facial phenotype which includes bitemporal narrowing, upslanting palpebral fissures, a short nose with anteverted nares, a broad and well demarcated philtrum, and large ears.HPE due to ZIC2 mutations is distinct from that due to mutations in other genes. This may shed light on the mechanisms involved in formation of the forebrain and face and will help direct genetic counselling and diagnostic strategies.

View details for DOI 10.1136/jmg.2009.073049

View details for Web of Science ID 000280274200002

View details for PubMedID 19955556

View details for PubMedCentralID PMC3208626