Expanded Clinical Spectrum of Autosomal-Dominant STT3A-CDG - PubMed
7 hours ago
- #dominant-negative
- #STT3A
- #congenital disorder of glycosylation
- STT3A-CDG is an autosomal-dominant disorder linked to the catalytic subunit of the OST-A complex.
- Abnormal transferrin glycosylation was present in nearly all cases (20/21).
- Common features include subtle facial dysmorphism and neurodevelopmental delays such as motor and speech delays, learning difficulties, and intellectual disability.
- Frequent musculoskeletal manifestations involve skeletal abnormalities, short stature, muscle cramps, and early-onset osteoarthritis.
- Less common features are congenital heart defects and coagulation factor deficiency.
- Newly reported individuals exhibited previously unreported features like anorectal malformation, morbid obesity, and significant bleeding diathesis with von Willebrand factor and factor VIII deficiency.
- Biochemical testing shows variable transferrin patterns, and near-normal results do not exclude diagnosis.
- Variants cluster in conserved catalytic regions, with p.Arg405 identified as a mutational hotspot, suggesting a dominant-negative mechanism.