Molecular spectrum of autosomal recessive osteogenesis imperfecta in 93 Italian children with bone fragility: a monocentric experience.

PURPOSE: Osteogenesis imperfecta (OI) usually follows an autosomal dominant inheritance pattern. We aimed to explore the epidemiological impact of autosomal recessive OI in a pediatric population and expand the mutational repertoire in this cohort.

METHODS

We presented our six-year (2018–2024) monocentric next-generation sequencing diagnostic activity on 93 unrelated children with a suspicion of OI. Variants were classified according to the American College of Medical Genetics and Genomics recommendations.

RESULTS

(Likely) pathogenic variants (PLP) or variants of uncertain significance were identified in 61.3% cases (57/93), with conclusive results (i.e. a heterozygous PLP in dominant genes, or biallelic PLP in recessive genes) in 59.1% (55/93). According to age, the rate of conclusive results was 84.0% (21/25), 52.7% (24/46) and 45.4% (10/22) in individuals aged 0–3 years, 4–12 years and 13–16 years, respectively. Six individuals out of 55 (11.0%) with conclusive results had biallelic PLP variants in autosomal recessive genes, among which we found three novel variants in SERPINF1 and WNT1, and confirmed OI as a possible phenotype due to PLOD2 abnormalities.

CONCLUSIONS

In our cohort of 93 Italian patients with a suspicion of OI, autosomal recessive OI was epidemiologically significant. Such a diagnostic perspective represents the prerequisite to combine multiprofessional and extended genetic testing assessments in children with OI to improve their diagnosis, management and treatment.