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Fetal anomalies

Gene: KIDINS220

Green List (high evidence)
KIDINS220 (kinase D interacting substrate 220)
EnsemblGeneIds (GRCh38): ENSG00000134313
EnsemblGeneIds (GRCh37): ENSG00000134313
OMIM: 615759, Gene2Phenotype
KIDINS220 is in 10 panels

6 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 26 Sep 2024, 11:09 a.m. | Last Modified: 26 Sep 2024, 11:09 a.m.
Panel Version: 4.192
This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group. Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.
Panel Version: 4.36

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 29 Aug 2024, 8:33 p.m.
Last Modified: 29 Aug 2024, 8:33 p.m.
Panel version: 4.192

Lyn Chitty (Great Ormond Street NHS Foundation Trust)

Green List (high evidence)

VM, ACC, hydrops, arthrogryposis (AD is DD, postnatal). Green for AR phenotype
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.
Panel Version: 4.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cerebral ventriculomegaly; spastic paraplegia, intellectual disability, nystagmus, and obesity MONDO:0015007; Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296; limb contractures

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Arina Puzriakova (Genomics England Curator)

The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to Green. However, the mode of inheritance of 'BIALLELIC, autosomal or pseudoautosomal' was approved following NHS Genomic Medicine Service consideration.
Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.
Panel Version: 2.10
Comment on phenotypes: Added relevant phenotype now listed in OMIM (MIM# 619501)
Created: 18 Nov 2021, 4:19 p.m. | Last Modified: 18 Nov 2021, 4:19 p.m.
Panel Version: 1.813
Created: 18 Nov 2021, 4:19 p.m.
Last Modified: 18 Nov 2021, 4:19 p.m.
Panel version: 2.10

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Third family reported with bi-allelic variants and severe prenatal phenotype.
Created: 14 Mar 2021, 4:55 a.m. | Last Modified: 14 Mar 2021, 4:55 a.m.
Panel Version: 1.635

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
limb contractures; ventriculomegaly; stillbirth

Publications

Created: 14 Mar 2021, 4:55 a.m.
Last Modified: 14 Mar 2021, 4:55 a.m.
Panel version: 1.635

Eleanor Williams (Genomics England Curator)

I don't know

Comment on mode of inheritance: Changing mode of inheritance to Biallelic with a recommendation for a green rating for this mode of inhertiance as there are now 3 cases with biallelic inheritance and a fetal phenotype.
Created: 20 Mar 2021, 11:13 a.m. | Last Modified: 20 Mar 2021, 11:13 a.m.
Panel Version: 1.636
Comment on mode of inheritance: After consultation with the Genomics England clinical team changing the MOI rating to BOTH monoallelic and biallelic but leaving the amber rating with a recommendation for this gene to be discussed at the next GMS review with regards to the 2 biallelic cases and the partially supportive mouse model.
Created: 11 Mar 2021, 1:26 p.m. | Last Modified: 11 Mar 2021, 1:26 p.m.
Panel Version: 1.635
Comment on mode of inheritance: Reverting to Monoallelic MOI until consult with Genomics England clinical team.
Created: 3 Mar 2021, 9:22 p.m. | Last Modified: 3 Mar 2021, 9:22 p.m.
Panel Version: 1.634
Comment on mode of inheritance: Changing MOI from monallelic to BOTH as 2 biallelic cases have now been reported with a more severe phenotype
Created: 3 Mar 2021, 9:13 p.m. | Last Modified: 3 Mar 2021, 9:13 p.m.
Panel Version: 1.632
Associated with Spastic paraplegia, intellectual disability, nystagmus, and obesity #617296 in OMIM for monoallelic cases.

2 biallelic cases associated with cerebral ventriculomegaly and limb contractures, plus a mouse model that shows some phenotypic overlap:

PMID: 33205811 - Jacquemin et al 2021 - report a consanguineous family of Pakistani origin in which 3 fetuses presented with brain ventriculomegaly and limb contractures. Autopsy of one fetus identifed bilateral club feet and club hands. They were found by WES to share a very rare homozygous variant of KIDINS220 (c.2327_2336del, Gln713_Leu715del). Parents and healthy siblings were heterozygous for this variant. Severe ventriculomegaly was diagnosed as early as 14 weeks. Binding of KIDINS220 to TrkA is decreased by the deletion mutation.

PMID: 28934391 - Mero et al 2017 - report a consanguineous couple in which 4 fetuses presented with enlarged cerebral ventricles and limb contractures. Exome sequencing in two of the fetuses found a shared homozygous frameshift variant in exon 24 in KIDINS220 ((NM_020738:c.3394_3403del; p.Gln1132Serfs*30). Healthy family members were either carriers or homozygous for the wild-type allele. It is thought that the variant leads to NMD and complete loss of KIDINS220 protein.

PMID: 22048169 - Cesca et al 2011 - report a Kidins220 mutant mouse. Kidins220 -/- mice die at late stages of gestation and show extensive neuronal cell death in the central and peripheral nervous systems, as well as heart malformations.
Created: 3 Mar 2021, 8:47 p.m. | Last Modified: 3 Mar 2021, 9 p.m.
Panel Version: 1.630

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
cerebral ventriculomegaly; limb contractures

Publications

Created: 3 Mar 2021, 8:47 p.m.
Last Modified: 3 Mar 2021, 9 p.m.
Panel version: 1.630

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable for Spastic paraplegia, intellectual disability, nystagmus, and obesity.
Created: 11 Dec 2018, 9:05 a.m.
Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.9

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • PAGE DD-Gene2Phenotype
Phenotypes
  • Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296
  • cerebral ventriculomegaly
  • limb contractures
OMIM
615759
Clinvar variants
Variants in KIDINS220
Penetrance
None
Publications
Panels with this gene

History Filter Activity

26 Sep 2024, Gel status: 3

Removed Tag, Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_24_promote_green was removed from gene: KIDINS220. Tag Q3_24_NHS_review was removed from gene: KIDINS220. Tag to_be_confirmed_NHSE was removed from gene: KIDINS220.

26 Sep 2024, Gel status: 3

Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to KIDINS220. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

30 Aug 2024, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: KIDINS220 were changed from Ventriculomegaly and arthrogryposis, OMIM:619501 to Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296; cerebral ventriculomegaly; limb contractures

30 Aug 2024, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: KIDINS220 were set to 33205811; 28934391; 22048169

30 Aug 2024, Gel status: 2

Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_24_promote_green tag was added to gene: KIDINS220. Tag Q3_24_NHS_review tag was added to gene: KIDINS220.

27 Dec 2023, Gel status: 2

Removed Tag, Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_21_rating was removed from gene: KIDINS220. Tag Q2_21_expert_review was removed from gene: KIDINS220. Tag Q2_21_MOI was removed from gene: KIDINS220.

30 Jan 2023, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag to_be_confirmed_NHSE tag was added to gene: KIDINS220.

30 Jan 2023, Gel status: 2

Added New Source

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to KIDINS220.

13 Dec 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_expert_review tag was added to gene: KIDINS220.

18 Nov 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296; spastic paraplegia, intellectual disability, nystagmus, and obesity MONDO:0015007; cerebral ventriculomegaly; limb contractures to Ventriculomegaly and arthrogryposis, OMIM:619501

20 Mar 2021, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: KIDINS220 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

11 Mar 2021, Gel status: 2

Added Tag, Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: KIDINS220. Tag Q2_21_MOI tag was added to gene: KIDINS220.

11 Mar 2021, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: KIDINS220 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

3 Mar 2021, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: KIDINS220 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Mar 2021, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity. to Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296; spastic paraplegia, intellectual disability, nystagmus, and obesity MONDO:0015007; cerebral ventriculomegaly; limb contractures

3 Mar 2021, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: KIDINS220 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

3 Mar 2021, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: KIDINS220 were set to

8 Nov 2018, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: KIDINS220 was added gene: KIDINS220 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: KIDINS220 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: KIDINS220 were set to Spastic paraplegia, intellectual disability, nystagmus, and obesity.