Microcephaly

Gene: UFC1

Green List (high evidence)

Note the NM_016406.4:c.255+17G>A variant is relatively common disease-causing variant.

Created: 10 Oct 2024, 6:56 a.m. | Last Modified: 10 Oct 2024, 6:56 a.m.

Panel Version: 1.286

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spasticity and poor growth (MIM#618076)

Green List (high evidence)

PMID 29868776: 8 affected individuals from 4 families reported. 7 were described to be postnatally microcephalic (at or below 3rd percentile). One was -5.1SD and one was -3.6SD. SD values for the others weren't provided.

The following head circumference measurements were provided for 6 of the affecteds:

51cm at 16yo; 50cm at 19yo; 42.5cm at 12mo, 45cm at 28mo, 45.2cm at 7yo; 45cm at 4yo.

3 of the families were consanguineous Saudi families with the same homozygous missense variant.

In vitro functional expression studies showed that both mutations caused impaired thioester binding with UFM1. Patient cells also showed decreased UFC1 intermediate formation with UFM1. The decrease in function was consistent with a hypomorphic allele, and the authors suggested that complete loss of function would be embryonic lethal.

PMID 30552426: 1 more individual with epileptic encephalopathy reported with a different homozygous missense variant in UFC1. The patient had microcephaly <3rd percentile.

Sources: Literature

Created: 2 Sep 2020, 4:08 a.m. | Last Modified: 2 Sep 2020, 6:36 a.m.

Panel Version: 0.309

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spasticity and poor growth (MIM#618076)

Publications

• 29868776
• 30552426

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