A Novel Homozygous Splice Variant in the NUP188 Gene Causing Sandestig-Stefanova Syndrome in a Saudi Patient.

PMID 40859750 | DOI 10.1002/ajmg.a.64236 · American journal of medical genetics. Part A · 2026 · View on PubMed ↗

Sandestig-Stefanova syndrome (SANDSTEF) (OMIM: 618804) is a recently identified autosomal recessive disorder characterized by a complex phenotype affecting multiple organ systems. To date, only 10 cases have been reported in the literature. Here, we present a newly identified patient exhibiting a distinct clinical presentation, along with a novel homozygous splice variant in NUP188. The proband has multiple system involvement, including ophthalmology, central nervous system, skin, distinct facial features, congenital heart disease, and respiratory system; eventually, he passed away with respiratory failure. A novel splice variant was identified using ES (NM_015354.2c.1962-2A>C p.(?)). The variant was confirmed by Sanger sequencing and was found to segregate from the parents. RT-PCR analysis showed no detectable amplification in the proband, while parental samples displayed two bands, indicating carrier status. The identification of a novel pathogenic variant contributes to a deeper understanding of the molecular mechanisms underlying the disorder and expands its phenotypic spectrum.