Locus HPE5 ZIC2

0.05-0.23/100,000; math done by 40% of pathogenic variants in ZIC2 are expansion²; 5% of non-syndromic HPE are ZIC2 gene², and nonsyndromic HPE is 25-50% of HPE, which affects 1/10,000 newborns³- ZIC2 is 9.2% of HPE cases, which occur in 1/16,000 live births⁴. Holoprosencephaly has worldwide distribution⁵, but STR-specific distribution is unknown.

Age of Onset

HPO Terms

–

Association

Mendelian

Locus

hg19 chr13:100637702-100637748

hg38 chr13:99985448-99985494

t2t chr13:99196358-99196404

Details

The benign allele of 15 repeats expands to 25 repeats to cause disease⁶, although the expansion can potentially present with a mild phenotype⁷

Mechanism

LoF

Polyalanine expansion interfering with DNA binding and transcriptional activation^8,9.

Detection

Year

2001¹⁰

Location in Gene

Coding Exon 3

Gene Strand

Alleles

Ref. Motif

GCN

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GCN

Pathogenic (gene)

CNG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0012322

Holoprosencephaly Overview

Cedrik,Tekendo-Ngongang, Maximilian,Muenke, Paul,Kruszka

GeneReviews® · 1993-01-01

genereviews:NBK1530

Nonsyndromic holoprosencephaly: MedlinePlus Genetics

url:medlineplus.gov/genetics/condition/nonsyndromic-holoprosencephaly/

Holoprosencephaly.

Christèle,Dubourg, Claude,Bendavid, Laurent,Pasquier, Catherine,Henry, Sylvie,Odent, Véronique,David

Orphanet journal of rare diseases · 2007-02-02

pmid:17274816

Vérification de la connexion...

orphanet:2162

POLYALANINE TRACT DISORDERS AND NEUROCOGNITIVE PHENOTYPES

Cheryl,Shoubridge, Jozef,Gecz

Madame Curie Bioscience Database [Internet] · 2013-01-01

genereviews:NBK51932

P703: Pathogenic ZIC2 polyalanine expansion detected by exome sequencing in a family with multi-generation holoprosencephaly

Nichole,Owen, Liesbeth,Vossaert, Lorraine,Potocki, Elizabeth,Mizerik

Genetics in Medicine Open · 2024-01-01

doi:10.1016/j.gimo.2024.101607

The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism.

Erich,Roessler, Felicitas,Lacbawan, Christèle,Dubourg, Aimee,Paulussen, Jos,Herbergs, Ute,Hehr, Claude,Bendavid, Nan,Zhou, Maia,Ouspenskaia, Sherri,Bale, Sylvie,Odent, Vèronique,David, Maximilian,Muenke

Human mutation · 2009-04-01

pmid:19177455

In vitro analysis of partial loss-of-function ZIC2 mutations in holoprosencephaly: alanine tract expansion modulates DNA binding and transactivation.

Lucia,Brown, Melinda,Paraso, Ruth,Arkell, Stephen,Brown

Human molecular genetics · 2004-12-08

pmid:15590697

Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination.

L Y,Brown, S,Odent, V,David, M,Blayau, C,Dubourg, C,Apacik, M A,Delgado, B D,Hall, J F,Reynolds, A,Sommer, D,Wieczorek, S A,Brown, M,Muenke

Human molecular genetics · 2001-04-01

pmid:11285244

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Identification of a novel non-coding deletion in Allan-Herndon-Dudley syndrome by long-read HiFi genome sequencing.

Jihoon G,Yoon, Seungbok,Lee, Soojin,Park, Se Song,Jang, Jaeso,Cho, Man Jin,Kim, Soo Yeon,Kim, Woo Joong,Kim, Jin Sook,Lee, Jong-Hee,Chae

BMC medical genomics · 2025-03-03

pmid:40033291