Supplementary Material for: A Rare Pathogenic Variant in the <b><i>SERPINF1</i></b> Gene in Association with Early-Onset Severe Presentation of Autosomal Recessive Type of Osteogenesis Imperfecta VI: A Case Report

Osteogenesis imperfecta (OI) refers to a group of genetic disorders with the typical clinical presentation of increased bone fragility. More than 90% of OI cases have an underlying genetic mutation in the collagen genes <i>COL1A1</i> or <i>COL1A2</i>. However, there are now 22 different recognized OI subtypes based on the underlying gene implicated. OI type VI is caused by pathogenic variants in the serine proteinase inhibitor clade F (<i>SERPINF1</i>) gene. In this case study, the patient was a 4-year-old female, born in a consanguineous family, with a history of delayed gross motor milestones and recurrent fractures after trivial trauma since the age of 8 months. The results of skeletal surveys and bone scans indicated that the patient suffered from OI. To confirm the diagnosis, we performed a next-generation sequencing (NGS) analysis of genes implicated in OI using the TruSight One NGS Panel. Bioinformatics analysis showed the presence of a rare pathogenic variant in exon 7 of the <i>SERPINF1</i> gene in a homozygous state (NM_002615.5:c.907C&gt;T; NP_002606.3:p.Arg303Ter; ClinVar submission ID: SUB10491966). The variant results in the termination of the polypeptide chain at position 303. Targeted capillary sequencing confirmed the presence of this variant in a homozygous state in the patient and in heterozygous state for both parents. Additionally, the patient’s younger sibling, aged 10 months, harbored the variant in a homozygous state. The sibling started bisphosphonate therapy and did not suffer any fractures in over 2 years after initiating the therapy. The etiological genetic diagnosis helped provide genetic counseling to the family. This highlights the utility of NGS for the confirmation of a clinical analysis in cases where alterations in multiple genes can result in similar clinical presentation.