Congenital Heart Defect

Gene: NUP188

Green List (high evidence)

Sandestig et al 2020/19:
two unrelated female infants from consanguineous families, each with homozygous nonsense gene variants of NUP188 (p.Tyr96* and p.Gln113*, respectively). Both patients showed close similarity and specificity of clinical features including the course of the disease and a poor prognosis.

Muir et al 2020:
Four unrelated families with six affected female infants with bi-allelic truncating variants in NUP188. all found to have very similar phenotypes
Functional studies showed:
1. Nuclear import of proteins was decreased in affected individuals’ fibroblasts, supporting a possible disease mechanism.
2. CRISPR-mediated knockout of NUP188 in Drosophila revealed motor deficits and seizure susceptibility, partially recapitulating the neurological phenotype seen in affected individuals.
3. Removal of NUP188 also resulted in aberrant dendrite tiling, suggesting a potential role of NUP188 in dendritic development

Key clinical features of Sandestig-Stefanova syndrome MIM 618804:
- congenital cataracts
- hypotonia,
- prenatal-onset ventriculomegaly,
- white-matter abnormalities,
- hypoplastic corpus callosum,
- congenital heart defects, and
- central hypoventilation. 
Characteristic dysmorphic features include:
- small palpebral fissures,
- a wide nasal bridge and nose,
- micrognathia, and
- digital anomalies.
Sources: Literature

Created: 20 Nov 2023, 3:57 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sandestig-Stefanova syndrome MIM 618804

Publications

• PMID: 32021605
• 32275884