Fetal anomalies
Gene: KIDINS220The 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
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
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 phenotypeCreated: 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
DDG2P rating in original PAGE list: Probable for Spastic paraplegia, intellectual disability, nystagmus, and obesity.Created: 11 Dec 2018, 9:05 a.m.
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.
Tag to_be_confirmed_NHSE tag was added to gene: KIDINS220.
Source NHS GMS was added to KIDINS220.
Tag Q2_21_expert_review tag was added to gene: KIDINS220.
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
Mode of inheritance for gene: KIDINS220 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Tag Q2_21_rating tag was added to gene: KIDINS220. Tag Q2_21_MOI tag was added to gene: KIDINS220.
Mode of inheritance for gene: KIDINS220 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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
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
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
Publications for gene: KIDINS220 were set to
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.