Department of Orthopaedics and Traumatology, Health Sciences University, Trabzon Kanuni Training and Research Hospital, Turkey.
Department of Pediatric Endocrinology, Faculty Of Medicine, Health Sciences University, Trabzon Kanuni Training and Research Hospital, Turkey.
Adv Clin Exp Med. 2021 Dec;30(12):1233-1238. doi: 10.17219/acem/141367.
Osteogenesis imperfecta (OI) is a genetic disorder that causes skeletal fragility, multiple fractures and several extraskeletal disorders. Most cases of OI are caused by mutations in COL1A1/A2. Osteogenesis imperfecta type VIII typically causes a severe and fatal phenotype that presents at birth with severe osteopenia, congenital fractures and other clinical manifestations.
We describe the cases of an 11-year-old female and a 9-year-old male with homozygous truncating mutations in P3H1. Both cases were born with intrauterine fractures and suffered multiple fractures shortly after birth, requiring multiple operations to correct both fractures and severe scoliosis. The patients have been treated with pamidronate since the age of 2.
Whole exome sequencing (WES) was performed by Gene by Gene using Twist Bioscience technology. Initially, ~36.5 Mb of consensus coding sequences (targeting >98% of RefSeq and Gencode v. 28 regions obtained from the human genome) was replicated from fragmented genomic DNA using the Twist Human Core Exome Plus kit. The subsequent library was sequenced on the Illumina Novaseq Next Generation Sequencing platform to achieve at least ×20 reading depth for >98% of the targeted bases. Variant annotations and filtering was performed using Ingenuity Variant Analysis software.
We identified a homozygous mutation in the 3rd exon of P3H1 (c.628C>T/p.Arg210 Ter). Our cases broaden the phenotypic spectrum of OI type VIII as, to the best of our knowledge, these are the first postnatal cases with P3H1 (c.628C>T/p.Arg210 Ter) mutations published in the literature.
We present the first recorded postnatal cases from unrelated families of OI type VIII, broadening our understanding of the severe, but nonfatal spectrum of clinical phenotype of this recessive form of OI.
成骨不全症（OI）是一种遗传性疾病，可导致骨骼脆弱、多发性骨折和多种骨骼外疾病。大多数 OI 病例是由 COL1A1/A2 基因突变引起的。OI 类型 VIII 通常导致严重和致命的表型，在出生时表现为严重的骨质疏松症、先天性骨折和其他临床表现。
我们描述了两名患有同源截短突变 P3H1 的 11 岁女性和 9 岁男性的病例。这两个病例都在宫内骨折，并在出生后不久遭受多次骨折，需要多次手术来矫正骨折和严重的脊柱侧弯。患者从 2 岁开始接受帕米膦酸盐治疗。
全外显子组测序（WES）通过 Gene by Gene 使用 Twist Bioscience 技术进行。最初，使用 Twist Human Core Exome Plus 试剂盒从碎片化的基因组 DNA 中复制出约 36.5 Mb 的共识编码序列（靶向来自人类基因组的 >98%RefSeq 和 Gencode v.28 区域）。随后的文库在 Illumina Novaseq 下一代测序平台上进行测序，以实现 >98%靶向碱基的至少 ×20 读深度。使用 Ingenuity Variant Analysis 软件进行变异注释和筛选。
我们在 P3H1 的第 3 外显子中发现了一个纯合突变（c.628C>T/p.Arg210 Ter）。我们的病例拓宽了 OI 类型 VIII 的表型谱，因为据我们所知，这些是文献中首次报道的 P3H1（c.628C>T/p.Arg210 Ter）突变的产后病例。
我们提出了来自无关家族的 OI 类型 VIII 的首例记录的产后病例，拓宽了我们对这种隐性 OI 严重但非致命临床表型谱的理解。
