Holoprosencephaly 5 (ZIC2)
| Dred_ID | RD00023 |
| OMIM ID | 609637 |
| Disease name | Holoprosencephaly 5 |
| Alternative names | HPE5 |
| Category | Rare diseases, Neuronal diseases, Endocrine diseases, Fetal diseases, Genetic diseases |
| Phenotype | NIH Rare Diseases: Holoprosencephaly is an abnormality of brain development in which the brain doesn't properly divide into the right and left hemispheres. The condition can also affect development of the head and face. There are 4 types of holoprosencephaly, distinguished by severity. From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In general, the severity of any facial defects corresponds to the severity of the brain defect. The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is only partially divided, and the eyes usually are set close together. Other signs and symptoms often include intellectual disability and pituitary gland problems. Holoprosencephaly can be caused by mutations in any of at least 14 different genes; chromosome abnormalities; or agents that can cause birth defects (teratogens). It may also be a feature of several unique genetic syndromes. In many cases, the exact cause is unknown. Life expectancy for people with this condition varies, and treatment depends on the symptoms and severity in each person. |
| Miscellaneouse | high occurrence of de novo mutations subtle facial phenotype compared to other types of hpe |
| Prevalence | Prevalence: 1-5/10000 (Europe) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | N/A |
| Evidence | Weak |
| Gene symbol | ZIC2 |
| Alias symbols | HPE5 |
| Gene name | Zic family member 2 |
| Gene map locus | 13q32; chr13:99,981,784-99,986,765(+) |
| Ensembl Gene ID | ENSG00000043355 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Expansion of an alanine repeat in the C-terminus of the encoded protein and other mutations in this gene cause holoprosencephaly type 5. Holoprosencephaly is the most common structural anomaly of the human brain. A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects. This gene is closely linked to a gene encoding zinc finger protein of the cerebellum 5, a related family member on chromosome 13. [provided by RefSeq, Jul 2016] |
| Repeat unit | GCG |
| Normal repeat copies | 15 |
| Pathogenic repeat copies | ≥25 |
| Gene | ZIC2 |
| Repeat location | CDS |
| Chromosome locus | chr13:99985449-99985496 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | Brown et al. (2001) found 15 ZIC2 mutations within a cohort of 509 isolated holoprosencephaly cases. Seven mutations were frameshifts that were predicted to result in loss of function, further supporting the idea that ZIC2 haploinsufficiency can result in HPE. One mutation, an alanine tract expansion which is caused by the expansion of an imperfect trinucleotide repeat, occurred in 7 patients from 6 different families. In 3 of those families, the father was found to be apparently mosaic for the mutation. The authors hypothesized that this mutation may arise through errors in somatic recombination, an extremely unusual mutation mechanism. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 11285244 |
| Authors | Brown LY, Odent S, David V, Blayau M, Dubourg C, Apacik C, Delgado MA, Hall BD, Reynolds JF, Sommer A, Wieczorek D, Brown SA, Muenke M |
| Title | Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination |
| Journal | Hum Mol Genet. 10(8):791-6 |
| Year | 2001 |