Non-syndromic familial congenital anorectal malformations

Gene: ZIC3

Green List (high evidence)

ZIC3 (Zic family member 3)
EnsemblGeneIds (GRCh38): ENSG00000156925
EnsemblGeneIds (GRCh37): ENSG00000156925
OMIM: 300265, Gene2Phenotype
ZIC3 is in 16 panels

2 reviews

Charles Shaw-Smith (Royal Devon and Exeter NHS Trust)

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Eleanor Williams (Genomics England Curator)

Comment when marking as ready: Gene checked.
Created: 1 Nov 2018, 12:34 p.m.
Gene is on expert list from Dr Charles Shaw-Smith (Royal Devon and Exeter NHS Foundation Trust)
Created: 19 Sep 2018, 4:21 p.m.
Comment on publications: Added phenotypes from papers reported in Hilger et al.
Created: 6 Sep 2018, 3:53 p.m.
Comment on list classification: Rating this gene green as ZIC3 variants have been found in more than 3 families with VACTERL or VACTERL-like phenotypes that include anorectal malformations.
Created: 6 Sep 2018, 3:51 p.m.
Gene added to panel as found to be candidate gene by Hilger et al 2015 (PMID: 26294094) who performed targeted sequencing of 123 patients with VATER/VACTERL or VATER/VACTERL-like phenotype. All patients had anorectal malformations. They identified an identical, probably disease-causing ZIC3 missense mutation (p.Gly17Cys) in four patients from 3 families. 2 patients also had other mutations (in IFT57 and TTC21B). The amino acid change is in a highly conserved residue and predicted to be deleterious in 4 out of 5 prediction algorithms. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures. Hilger et al 2015 also report that ZIC3 deletion/variants were found in patients from 5 other families with VATER/VACTERL or VATER/VACTERL-like association without hydrocephalus but with anorectal malformations (Purandare et al., 1999, Ware et al., 2004 (PMID: 14681828), Wessels et al., 2010 (PMID: 20452998), Chung et al., 2011 (PMID: 21465648)). The gene is also on the Illumina panel for VACTERL Association, X-linked. ZIC3 is listed as associated with "VACTERL association, X-linked" in OMIM, and anal atresia is a phenotype for this disorder.
Created: 4 Aug 2018, 10:12 p.m.

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Expert list
  • Other
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • anorectal malformation
  • VACTERL ASSOCIATION, X-LINKED, WITH OR WITHOUT HYDROCEPHALUS
  • VACTERL Association, X-linked 314390
  • VACTERLX 314390
OMIM
300265
Clinvar variants
Variants in ZIC3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

8 Nov 2018, Gel status: 4

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

Eleanor Williams: Gene added to panel as found t

1 Nov 2018, Gel status: 4

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: ZIC3 were changed from anorectal malformation; VACTERL ASSOCIATION, X-LINKED, WITH OR WITHOUT HYDROCEPHALUS; VACTERL Association, X-linked; VACTERLX 314390 to anorectal malformation; VACTERL ASSOCIATION, X-LINKED, WITH OR WITHOUT HYDROCEPHALUS; VACTERL Association, X-linked 314390; VACTERLX 314390

1 Nov 2018, Gel status: 4

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: zic3 has been classified as Green List (High Evidence).

19 Sep 2018, Gel status: 4

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes anorectal malformation for gene: ZIC3

19 Sep 2018, Gel status: 4

Added New Source, Set Phenotypes

Eleanor Williams (Genomics England Curator)

Source Expert list was added to ZIC3. Added phenotypes anorectal malformation for gene: ZIC3

6 Sep 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: ZIC3 were set to 26294094; 14681828; 20452998; 21465648

6 Sep 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: zic3 has been classified as Green List (High Evidence).

14 Aug 2018, Gel status: 1

Added New Source, Set penetrance

Eleanor Williams (Genomics England Curator)

Other was added to ZIC3. Panel: Non-syndromic familial congenital anorectal malformations Phenotypes for gene ZIC3 were set to VACTERL Association, X-linked, VACTERL ASSOCIATION, X-LINKED, WITH OR WITHOUT HYDROCEPHALUS, VACTERLX 314390

14 Aug 2018, Gel status: 1

Added New Source, Set publications

Eleanor Williams (Genomics England Curator)

Literature was added to ZIC3. Panel: Non-syndromic familial congenital anorectal malformations Publications for gene ZIC3 was set to ['26294094']

14 Aug 2018, Gel status: 1

Set penetrance

Eleanor Williams (Genomics England Curator)

Phenotypes for gene ZIC3 were set to VACTERL Association, X-linked

3 Aug 2018, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

ZIC3 was added to Non-syndromic familial congenital anorectal malformations panel. Sources: Illumina TruGenome Clinical Sequencing Services

3 Aug 2018, Gel status: 1

Created

Eleanor Williams (Genomics England Curator)

ZIC3 was created by Eleanor Williams