Biallelic variants in SPARC are extremely rare, and have been reported in only a few cases of autosomal recessive osteogenesis imperfecta (OI) type XVII. Here, we describe an individual with a SPARC homozygous missense variant (c.787G > A; p.Glu263Lys) and expand on the phenotype. The proband had a history of multiple fractures, osteopenia, severe thoracolumbar levoscoliosis, rib fusion, global hypotonia, conductive hearing loss, and was non-ambulatory. Several of his features were similar to previously described cases, such as early neuromuscular concerns, scoliosis, long bone and vertebral compression fractures, and delayed motor milestones, suggesting these are consistent across SPARC-related osteogenesis imperfecta (OI). However, the proband sustained fractures at a younger age with a more severe course compared to most previous reports. He also had bony fusion of several ribs and hearing loss, which have not been reported in SPARC-related OI. Overall, the proband supports the current phenotype of SPARC-related OI, but also expands the phenotypic variability.

中文翻译：

---

XVII 型成骨不全症：表型的扩展

SPARC 中的双等位基因变异极为罕见，仅在少数 XVII 型常染色体隐性成骨不全症 (OI) 病例中报道过。在这里，我们描述了具有 SPARC 纯合错义变异（c.787G > A；p.Glu263Lys）的个体，并扩展了表型。先证者有多处骨折、骨质减少、严重胸腰椎左脊柱侧凸、肋骨融合、整体肌张力减退、传导性听力损失的病史，并且不能行走。他的一些特征与之前描述的病例相似，例如早期神经肌肉问题、脊柱侧凸、长骨和椎体压缩骨折以及运动里程碑延迟，表明这些特征在 SPARC 相关的成骨不全症 (OI) 中是一致的。然而，与之前的大多数报告相比，先证者在更年轻的时候就发生了骨折，并且病程更严重。他还患有多根肋骨骨融合和听力损失，这在 SPARC 相关的成骨不全症中尚未有报道。总体而言，先证者支持 SPARC 相关 OI 的当前表型，但也扩大了表型变异性。