Akademik Veri Yönetim Sistemi
JOURNAL OF HUMAN GENETICS, 2025 (SCI-Expanded, Scopus)
SEC24D is a key component of the Coat Protein Complex II, which plays a critical role in the selective sorting and transport of cargo proteins from the endoplasmic reticulum. This function is particularly essential for the secretion of extracellular matrix proteins, including collagens. Biallelic pathogenic variants in SEC24D have been associated with Cole-Carpenter Syndrome 2, a rare skeletal dysplasia characterized by craniofacial abnormalities and recurrent fractures. We reported a 12-year-old male patient presenting with recurrent bone fractures, severe skeletal deformities, limb shortening, craniofacial dysmorphism and pseudoarthrosis, a feature not previously reported in this condition. Whole-exome sequencing identified a novel homozygous synonymous variant in SEC24D (c.2361C>T; p.Asn787=), located 16 bases upstream of the donor splice site of intron 18. Functional analyses revealed markedly reduced SEC24D expression and aberrant exon 18 skipping, supported by RNA-seq, qPCR, and Western blot. This case provided the first functional evidence for a synonymous variant in SEC24D causing disease via splicing disruption and expands both the phenotypic and genotypic spectrum of Cole-Carpenter Syndrome 2.