Fetal anomalies
Gene: UNC80

UNC80 (unc-80 homolog, NALCN channel complex subunit)
EnsemblGeneIds (GRCh38): ENSG00000144406
EnsemblGeneIds (GRCh37): ENSG00000144406
OMIM: 612636, Gene2Phenotype
UNC80 is in 10 panels

3 reviews

Ain Roesley (Victorian Clinical Genetics Services)

I don't know

2 remotely related consanguineous families with 7 affecteds. born at term, following uneventful pregnancies, with various
degrees of IUGR (birth weights 1900–2700 g).
Homozygous R51* found via WES and confirmed to segregate via Sanger
Created: 9 Mar 2022, 5:44 a.m. | Last Modified: 9 Mar 2022, 5:44 a.m.

Panel Version: 1.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777

Publications

26545877

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

Created: 9 Mar 2022, 5:44 a.m.
Last Modified: 9 Mar 2022, 5:44 a.m.
Panel version: 1.7

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

UNC80 is part of the NALCN complex, and this is considered a NALCN channelopathy.

More than 20 individuals from more than 5 unrelated families reported with bi-allelic variants in this gene and severe autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy. Affected individuals show severe global developmental delay with poor or absent speech and absent or limited ability to walk. Some have had seizures; brain structure is typically normal.

UNC80 knockout mice are neonatal lethal.
Created: 4 Nov 2020, 9:24 p.m. | Last Modified: 4 Nov 2020, 9:24 p.m.

Panel Version: 0.3174

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777

Publications

Created: 4 Nov 2020, 9:24 p.m.
Last Modified: 4 Nov 2020, 9:24 p.m.
Panel version: 0.3969

Paul De Fazio (Victorian Clinical Genetics Services)

Green List (high evidence)

Summary: Many patients reported as microcephalic. Not all have head circumference < -3SD but there are at least 3 unrelated individuals reported with head circumference smaller than this.

PMID 26708751: 4 individuals from 3 families reported. At 4 years one had OFC -4SD (the others 2nd centile at 4yo, 3rd centile at 15yo, and 10th centile at 9yo).

PMID 26708753: Two 'not directly related' families F1 and F2 identified with the same variant. A third and fourth family had different variants. All affected individuals described were microcephalic (F1: -3.2SD at 4yo; F2: -4SD at 2yo and -2.9SD at 13mo; F3: -2.4SD at 7yo; F4: 9th centile at 4yo and 5th centile at 8yo).

PMID 26545877: 7 affected individuals from 2 distantly related families with the same nonsense variant were all microcephalic (<2nd centile).

PMID 29572195: 2 unrelated individuals reported. Head circumference of patient 1 was -0.5SD at 9yo; Patient 2 -3.7SD at 3yo.
Created: 2 Sep 2020, 2:41 a.m. | Last Modified: 2 Sep 2020, 2:41 a.m.

Panel Version: 0.273

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 MIM#616801

Publications

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

Created: 2 Sep 2020, 2:41 a.m.
Last Modified: 2 Sep 2020, 2:41 a.m.
Panel version: Imported from Microcephaly panel version 0.273

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Genomics England PanelApp
Genetic Health Queensland

Phenotypes

Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801
MONDO:0014777

OMIM

612636

Clinvar variants

Variants in UNC80

Penetrance

None

Publications

Panels with this gene