Characterization of three adults and an adolescent with Osteogenesis Imperfecta type VI and a novel founder SERPINF1 variant

• Published in: European journal of medical genetics 2023-11, Vol.66 (11), p.104867-104867, Article 104867
• Main Authors: Travessa, André M., Dias, Patrícia, Rosmaninho-Salgado, Joana, Aza-Carmona, Miriam, Moldovan, Oana, Díaz‐González, Francisca, Godinho, Fátima, Romeu, José Carlos, Oliveira-Ramos, Filipa, do Céu Barreiros, Maria, Sousa, Sérgio B., Heath, Karen E., Sousa, Ana Berta
• Format: Article
• Language: English
• Subjects: Autosomal recessive; Bone fragility; Osteogenesis imperfecta; Osteogenesis imperfecta type VI; Pigment epithelium-derived factor (PEDF); SERPINF1
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2023.104867

Osteogenesis imperfecta (OI) type VI is an extremely rare form of OI caused by biallelic variants in the SERPINF1 gene, which codes for the pigment-epithelium derived factor (PEDF). We report on four patients (three adults and one adolescent) with a severe deforming form of OI. All patients presented no abnormalities at birth, frequent long bone and vertebrae fractures (mainly during childhood), marked short stature, severe bone deformities, chronic mild to moderate pain, and severe limitation of mobility, with three being completely wheelchair bound. Blue sclera and dentinogenesis imperfecta were absent, although some patients presented tooth, ophthalmological, and/or cardiac features. Radiographic findings included, among others, thin diaphysis and popcorn calcifications, both of which are non-specific to this type of OI. The novel homozygous variants c.816_819del (p.Met272Ilefs*8) and c.283+2T > G in SERPINF1 were identified in three and one patient, respectively. The three patients carrying the frameshift variant were born in nearby regions suggesting a founder effect. Describing the long-term outcomes of four patients with OI type VI, this cohort adds relevant data on the clinical features and prognosis of this type of OI.