Locus VACTERLX ZIC3

VACTERL is an acronym for vertebral anomalies (similar to those of spondylocostal dysplasia), anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies (urethral atresia with hydronephrosis), and limb anomalies¹.

Prevalence

Found in one patient²with European ancestry³.

Age of Onset

HPO Terms

–

Association

Mendelian

Locus

hg19 chrX:136648985-136649015

hg38 chrX:137566826-137566856

t2t chrX:135876774-135876804

Details

Frequently genotyped as (NGC)*, although locus structure has been reported as (GCC)8(GCT)(GCC)⁴. 1 patient with VACTERL died at birth with 12 repeats³. 8 patients with X-linked oculo-auriculo-vertebral spectrum (OAVS) had 11 repeats (intermediate allele size); 1 individual in OAVS cohort with 12 repeats; likely phenotypic spectrum⁵.

Mechanism

Unknown

Polyalanine expansion with unknown mechanism⁶.

Detection

Year

2010³

Location in Gene

Coding Exon 1

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

References

Direct supporting references for info on this page.

1omim:314390

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder?

Marja W,Wessels, Brian,Kuchinka, Rogier,Heydanus, Bert J,Smit, Dennis,Dooijes, Ronald R,de Krijger, Maarten H,Lequin, Elisabeth M,de Jong, Margreet,Husen, Patrick J,Willems, Brett,Casey

Journal of medical genetics · 2010-05-01

pmid:20452998

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3.

Aurélien,Trimouille, Angèle,Tingaud-Sequeira, Didier,Lacombe, Tina,Duelund Hjortshøj, Sven,Kreiborg, Hanne,Buciek Hove, Caroline,Rooryck

Clinical genetics · 2020-10-01

pmid:32639022

Expandable DNA repeats and human disease.

Sergei M,Mirkin

Nature · 2007-06-21

pmid:17581576

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)

Reanalysis of Next-Generation Sequencing Data to Detect Tandem Repeat Expansions in 1,106 Czech Probands With Neurologic Disease.

Alena,Musilova, Petra,Lassuthova, Anna,Uhrova Meszarosova, Barbora,Straka, Jana,Krejcikova, Anna,Berounska, Marketa,Vlckova, Zuzana,Musova, Dana,Safka Brozkova

Neurology. Genetics · 2025-06-25

pmid:40585427