Genotype-phenotype correlations in 294 pediatric patients with osteogenesis imperfecta.

IF 3.4 Q2 ENDOCRINOLOGY & METABOLISM JBMR Plus Pub Date : 2024-09-30 eCollection Date: 2024-11-01 DOI:10.1093/jbmrpl/ziae125
Jay J Byrd, Andrew C White, Claire G Nissen, Makayla Schissel, Matthew Van Ormer, Danita Velasco, Maegen Wallace
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Abstract

Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility with extraskeletal manifestations mostly due to COL1A1 and COL1A2 variants. Currently, 23 genes have been implicated in the pathogenesis of OI; however, literature on genotype-phenotype correlation and incidence of non-skeletal clinical features are limited. This study aims to identify genotype-phenotype correlations in patients with OI, allowing clinicians to better inform families of prognosis, optimize patient care, and facilitate evidence-based clinical decision-making. We retrospectively reviewed 294 patients with OI to collect demographic data, clinical characteristics, and genotypic information. Patients were stratified by COL1A1/1A2 vs non-COL1A1/1A2 variants to evaluate differences in phenotype. The majority of OI was due to variants in COL1A1/1A2 (91%), with the remaining 9% due to non-COL1A1/1A2 variants. Most patients in the COL1A1/2 group were White compared to the non-COL1A1/2 group (78% vs 50%; p = 0.004). COL1A/1A2 patients had higher incidence of blue sclerae (83% vs 58%, p = 0.002), dentinogenesis imperfecta (49% vs 15%, p < 0.001), and family history of OI (34% vs 12%, p = 0.03). Those in the non-COL1A1/1A2 group have higher rates of scoliosis compared to those in the COL1A1/1A2 group (62% vs 40%, p = 0.04), as well as higher rates of expressive language disorder/delay (15% vs 0.4% in non-COL1A1/1A2 and COL1A1/1A2 patients, respectively; p < 0.001). Identifying the underlying molecular etiology early is imperative for optimal clinical care, allowing for appropriate risk counseling, identification of affected relatives, and improved anticipatory care and management. These data support that rare subtypes of OI occur more frequently in non-White individuals and demonstrated genetic associations with incidence of blue sclera, dentinogenesis imperfecta, scoliosis, and expressive language disorders.

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294名儿童成骨不全症患者的基因型与表型之间的相关性。
成骨不全症(OI)是一种遗传性疾病,其特征是骨脆性和骨骼外表现,主要由 COL1A1 和 COL1A2 变体引起。目前,有 23 个基因被认为与 OI 的发病机制有关;然而,有关基因型与表型的相关性以及非骨骼临床特征发生率的文献却很有限。本研究旨在确定 OI 患者的基因型与表型之间的相关性,以便临床医生更好地告知家属预后、优化患者护理并促进循证临床决策。我们对 294 例 OI 患者进行了回顾性研究,收集了人口统计学数据、临床特征和基因型信息。根据 COL1A1/1A2 与非 COL1A1/1A2 变异对患者进行分层,以评估表型的差异。大多数 OI 是由 COL1A1/1A2 变异引起的(91%),其余 9% 是由非 COL1A1/1A2 变异引起的。与非 COL1A1/2 组相比,COL1A1/2 组的大多数患者是白人(78% vs 50%; p = 0.004)。COL1A/1A2 患者的蓝硬斑(83% 对 58%,P = 0.002)和牙本质发育不全(49% 对 15%,P = 0.03)发生率较高。与 COL1A1/1A2 组患者相比,非 COL1A1/1A2 组患者脊柱侧弯的发生率更高(62% vs 40%,P = 0.04),表达语言障碍/延迟的发生率也更高(非 COL1A1/1A2 和 COL1A1/1A2 患者分别为 15% vs 0.4%;P = 0.05)。
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来源期刊
JBMR Plus
JBMR Plus Medicine-Orthopedics and Sports Medicine
CiteScore
5.80
自引率
2.60%
发文量
103
审稿时长
8 weeks
期刊最新文献
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