Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: MINPP1

Amber List (moderate evidence)

MINPP1 (multiple inositol-polyphosphate phosphatase 1)
EnsemblGeneIds (GRCh38): ENSG00000107789
EnsemblGeneIds (GRCh37): ENSG00000107789
OMIM: 605391, Gene2Phenotype
MINPP1 is in 5 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: There is sufficient evidence to promote this gene to Green status at the next GMS panel update.

To date, at least 16 individuals from 10 unrelated families reported, all with different biallelic variants in MINPP1 (5 truncating, 6 missense). Main clinical characteristics included mild to severe PCH on brain MRI (16/16), moderate to severe DD/ID (16/16), microcephaly (14/16), and seizures (12/16). Supported by some functional data (PMIDs: 33257696; 33168985)
Created: 12 May 2021, 10:15 a.m. | Last Modified: 12 May 2021, 10:15 a.m.
Panel Version: 2.173

Zornitza Stark (Australian Genomics)

Green List (high evidence)

8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI.

Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions.
Sources: Literature
Created: 9 Dec 2020, 7:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Pontocerebellar hypoplasia
Tags
Q2_21_rating
OMIM
605391
Clinvar variants
Variants in MINPP1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 May 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: MINPP1.

12 May 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: MINPP1 were set to 33257696

12 May 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: minpp1 has been classified as Amber List (Moderate Evidence).

9 Dec 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: MINPP1 was added gene: MINPP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MINPP1 were set to 33257696 Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia Review for gene: MINPP1 was set to GREEN