Cerebellar and Pontocerebellar Hypoplasia

Gene: FTH1

Green List (high evidence)

FTH1 (ferritin heavy chain 1)
EnsemblGeneIds (GRCh38): ENSG00000167996
EnsemblGeneIds (GRCh37): ENSG00000167996
OMIM: 134770, Gene2Phenotype
FTH1 is in 5 panels

3 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodegeneration with brain iron accumulation 9, MIM# 620669

Bryony Thompson (Royal Melbourne Hospital)

Comment on list classification: Article describing the gene-disease association with neuroferritinopathy now published in HGG advances
Created: 4 Sep 2023, 10:50 p.m. | Last Modified: 4 Sep 2023, 10:50 p.m.
Panel Version: 1.61

Paul De Fazio (Victorian Clinical Genetics Services)

I don't know

Note paper is pre-print hence Amber rating.

5 unrelated paediatric patients presented with developmental delay, epilepsy, and progressive neurologic decline. All patients had pontocerebellar hypoplasia during infancy. Heterozygous nonsense FTH1 variants were identified by WES in all patients, 4 of which were confirmed de novo. All variants are predicted to escape NMD and appear to act by a dominant toxic gain-of-function mechanism. p.F171* was recurrent in three unrelated individuals.

Patient fibroblasts show elevated ferritin protein levels, markers of oxidative stress, and increased susceptibility to iron accumulation. Targeted knock-down of mutant FTH1 transcript with rescues cellular phenotypes.

Note NMD-escape variants in gnomAD exist, upstream of the variants in patients.
Sources: Literature
Created: 2 Mar 2023, 3:52 a.m. | Last Modified: 2 Mar 2023, 3:56 a.m.
Panel Version: 1.60

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Neuroferritinopathy (MONDO:0011638)

Publications

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Neurodegeneration with brain iron accumulation 9, MIM# 620669
OMIM
134770
Clinvar variants
Variants in FTH1
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

13 Jan 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669

4 Sep 2023, Gel status: 3

Set publications

Bryony Thompson (Royal Melbourne Hospital)

Publications for gene: FTH1 were set to 36778397

4 Sep 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: fth1 has been classified as Green List (High Evidence).

2 Mar 2023, Gel status: 2

Entity classified by Genomics England curator

Seb Lunke (Victorian Clinical Genetics Services)

Gene: fth1 has been classified as Amber List (Moderate Evidence).

2 Mar 2023, Gel status: 2

Entity classified by Genomics England curator

Seb Lunke (Victorian Clinical Genetics Services)

Gene: fth1 has been classified as Amber List (Moderate Evidence).

2 Mar 2023, Gel status: 0

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

Paul De Fazio (Victorian Clinical Genetics Services)

gene: FTH1 was added gene: FTH1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature Mode of inheritance for gene: FTH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FTH1 were set to 36778397 Phenotypes for gene: FTH1 were set to Neuroferritinopathy (MONDO:0011638) Mode of pathogenicity for gene: FTH1 was set to Other Review for gene: FTH1 was set to AMBER gene: FTH1 was marked as current diagnostic