Encyclopedia
Zic family member 2
- genes
1. Normal Function
The ZIC2 gene provides instructions for making a protein that plays an important role in the development of the front part of the brain (forebrain). This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. The ZIC2 protein regulates genes involved in both early and late stages of forebrain development.
2. Health Conditions Related to Genetic Changes
2.1. Nonsyndromic holoprosencephaly
More than 80 mutations in the ZIC2 gene have been found to cause nonsyndromic holoprosencephaly. This condition occurs when the brain fails to divide into two halves (hemispheres) during early development. ZIC2 gene mutations are the second most common cause of nonsyndromic holoprosencephaly. The facial features of individuals with ZIC2 gene mutations are different from those with nonsyndromic holoprosencephaly caused by mutations in other genes. These distinctive facial features include a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). It is unclear how mutations in the ZIC2 gene lead to these facial features.
ZIC2 gene mutations that cause nonsyndromic holoprosencephaly reduce or eliminate the activity of the ZIC2 protein. Without enough functional ZIC2 protein, the genes involved in normal forebrain development are not properly controlled. As a result, the brain does not separate into two hemispheres. The signs and symptoms of nonsyndromic holoprosencephaly are caused by abnormal development of the brain and face.
2.2. Coloboma
3. Other Names for This Gene
-
HPE5
-
Zic family member 2 (odd-paired Drosophila homolog)
-
Zic family member 2 (odd-paired homolog, Drosophila)
-
ZIC2_HUMAN
-
Zinc finger protein of the cerebellum 2
-
zinc finger protein ZIC 2
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/zic2
References
- Brown LY, Odent S, David V, Blayau M, Dubourg C, Apacik C, Delgado MA, HallBD, Reynolds JF, Sommer A, Wieczorek D, Brown SA, Muenke M. Holoprosencephaly dueto mutations in ZIC2: alanine tract expansion mutations may be caused by parentalsomatic recombination. Hum Mol Genet. 2001 Apr 1;10(8):791-6.
- Brown SA, Warburton D, Brown LY, Yu CY, Roeder ER, Stengel-Rutkowski S,Hennekam RC, Muenke M. Holoprosencephaly due to mutations in ZIC2, a homologue ofDrosophila odd-paired. Nat Genet. 1998 Oct;20(2):180-3.
- Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V.Holoprosencephaly. Orphanet J Rare Dis. 2007 Feb 2;2:8. Review.
- Roessler E, Lacbawan F, Dubourg C, Paulussen A, Herbergs J, Hehr U, BendavidC, Zhou N, Ouspenskaia M, Bale S, Odent S, David V, Muenke M. The full spectrumof holoprosencephaly-associated mutations within the ZIC2 gene in humans predictsloss-of-function as the predominant disease mechanism. Hum Mutat. 2009Apr;30(4):E541-54. doi: 10.1002/humu.20982.
- Roessler E, Muenke M. The molecular genetics of holoprosencephaly. Am J MedGenet C Semin Med Genet. 2010 Feb 15;154C(1):52-61. doi: 10.1002/ajmg.c.30236.Review.
- Solomon BD, Lacbawan F, Mercier S, Clegg NJ, Delgado MR, Rosenbaum K, Dubourg C, David V, Olney AH, Wehner LE, Hehr U, Bale S, Paulussen A, Smeets HJ, HardistyE, Tylki-Szymanska A, Pronicka E, Clemens M, McPherson E, Hennekam RC, Hahn J,Stashinko E, Levey E, Wieczorek D, Roeder E, Schell-Apacik CC, Booth CW, ThomasRL, Kenwrick S, Cummings DA, Bous SM, Keaton A, Balog JZ, Hadley D, Zhou N, Long R, Vélez JI, Pineda-Alvarez DE, Odent S, Roessler E, Muenke M. Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype andcomprehensive analysis of 157 individuals. J Med Genet. 2010 Aug;47(8):513-24.doi: 10.1136/jmg.2009.073049.
- Solomon BD, Mercier S, Vélez JI, Pineda-Alvarez DE, Wyllie A, Zhou N, Dubourg C, David V, Odent S, Roessler E, Muenke M. Analysis of genotype-phenotypecorrelations in human holoprosencephaly. Am J Med Genet C Semin Med Genet. 2010Feb 15;154C(1):133-41. doi: 10.1002/ajmg.c.30240. Review.
- Tekendo-Ngongang C, Muenke M, Kruszka P. Holoprosencephaly Overview. 2000 Dec 27 [updated 2020 Mar 5]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, BeanLJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA):University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1530/
- Warr N, Powles-Glover N, Chappell A, Robson J, Norris D, Arkell RM.Zic2-associated holoprosencephaly is caused by a transient defect in theorganizer region during gastrulation. Hum Mol Genet. 2008 Oct 1;17(19):2986-96.doi: 10.1093/hmg/ddn197.
