Video 1
Case presentation: clinical features of NUS1 and MEAD syndrome. The video shows the most relevant clinical features of a new case of myoclonus-epilepsy associated with a novel de novo missense variant of NUS1 (c.868C>T, p.R290C): speech is preserved; there is multifocal, mini-myoclonus of the face; eye movements only showed mild saccadic intrusion of pursuits; there is appendicular myoclonus involving the upper limbs, distally; there is no bradykinesia and only mild incoordination; there is action myoclonus that increases at target in both upper limbs; there is only mild appendicular ataxia and past-pointing; there is no stimulus-sensitive myoclonus; there is significant action myoclonus at approaching the paper with a pen and drawing a spiral; gait is narrow-based with no ataxia.
Figure 1
NUS1 pathogenic variants and related phenotypes. The figure summarizes the pathogenic variants reported in the literature in the NUS1 gene, highlighting their position on the gene, and associated phenotype: ataxia (orange), ID (light blue), or both (green) with epilepsy (upper part of the figure) or without epilepsy (lower part of the figure). Myoclonus was reported in all the listed variants except for c.869G>A (p.Arg290His) (homozygous), and c.743delA (p.Asp248Alafs). The only reported homozygous variant associated with CDG is bolded. Protein domains are labeled. TM: transmembrane. The new variant found in this report (likely pathogenic) is highlighted by the red box.
Figure 2
Brain MRI of the described case. The images show axial FLAIR (on the right) and coronal T1 (on the left) brain MRI imaging of this case, at age 25. Both images showed a mild cerebellar atrophy.
Table 1
Additional pathogenic NUS1 variants associated with CDG reported in ClinVar. Detailed phenotype description was not available for these variants.
| VARIANT | PROTEIN CHANGE | CONDITION(S) | CLINICAL SIGNIFICANCE | SOURCE |
|---|---|---|---|---|
| NM_138459.5(NUS1):c.15C>A (p.Tyr5Ter) | Y5* | Congenital disorder of glycosylation, type IAA | Pathogenic | ClinVar |
| NM_138459.5(NUS1):c.74_75delinsAA (p.Trp25Ter) | W25* | Congenital disorder of glycosylation, type IAA | Pathogenic | ClinVar |
| NM_138459.5(NUS1):c.74G>A (p.Trp25Ter) | W25* | Congenital disorder of glycosylation, type IAA | Pathogenic | ClinVar |
| NM_138459.5(NUS1):c.99dup (p.Asn34fs) | N34fs | Congenital disorder of glycosylation, type IAA | Pathogenic | ClinVar |
| NM_138459.5(NUS1):c.238_263del (p.Ala80fs) | A80fs | Intellectual disability, autosomal dominant 55, with seizures | Pathogenic | ClinVar |
| NM_138459.5(NUS1):c.415+1G>A | Intellectual disability, autosomal dominant 55, with seizures | Pathogenic | ClinVar | |
| NM_138459.5(NUS1):c.443T>A (p.Leu148Ter) | L148* | Inborn genetic diseases | Pathogenic | ClinVar |
| NM_138459.5(NUS1):c.719T>G (p.Leu240Ter) | L240* | Congenital disorder of glycosylation, type IAA | Pathogenic | ClinVar |