Research Centre for Medical Genetics, Moscow, Russia.
Mol Genet Genomic Med. 2021 Mar;9(3):e1620. doi: 10.1002/mgg3.1620. Epub 2021 Feb 11.
Stickler syndrome (STL) is a clinically variable and genetically heterogeneous collagenopathy characterized by ophthalmic, auditory, skeletal, and orofacial abnormalities. STL is mainly inherited in an autosomal dominant pattern with mutations in the COL2A1, COL11A1, and COL11A2 genes. Autosomal recessive forms are rare. However, 19 patients have been reported to date, with STL caused by homozygous or compound heterozygous mutations in genes that encode for the three chains of type IX collagen: COL9A1, COL9A2, and COL9A3.
Genetic analysis was performed using the next-generation sequencing of 166 genes associated with skeletal disorders and sequenced on an Ion Torrent S5 system with a minimum coverage of 100X. The two variants in the COL9A3 gene identified in the proband and the parents were confirmed by Sanger sequencing on an ABI3130xl sequencer.
We describe a novel case of autosomal recessive Stickler syndrome caused by two undescribed mutations in the COL9A3 gene: c.268C>T (p.Arg90Ter) and c.1729C>T (p.Arg577Ter). The clinical features included severe sensorineural hearing loss, high myopia, vitreoretinal degeneration, and early-onset arthropathy of the lower limbs. Radiography revealed mild spondyloepiphyseal dysplasia.
This case further expands the mutational and phenotypic spectrum of COL9A-associated STL with a more severe presentation.
成骨不全症（STL）是一种临床变异性和遗传异质性的胶原病，其特征为眼部、听觉、骨骼和口腔颌面部异常。STL 主要以常染色体显性遗传模式遗传，突变发生在 COL2A1、COL11A1 和 COL11A2 基因中。常染色体隐性形式很少见。然而，迄今为止已有 19 例报道，由于编码 III 型胶原的三个链的基因（COL9A1、COL9A2 和 COL9A3）中的纯合子或复合杂合突变而导致 STL。
使用与骨骼疾病相关的 166 个基因的下一代测序进行基因分析，并在 Ion Torrent S5 系统上进行测序，最小覆盖度为 100X。在先证者和父母中发现的 COL9A3 基因中的两个变体通过在 ABI3130xl 测序仪上进行 Sanger 测序进行了确认。
我们描述了一例由 COL9A3 基因中的两个未描述的突变引起的常染色体隐性成骨不全症的新病例：c.268C>T（p.Arg90Ter）和 c.1729C>T（p.Arg577Ter）。临床特征包括严重的感音神经性听力损失、高度近视、玻璃体视网膜变性和下肢早发性关节炎。放射学显示轻度脊椎骨骺发育不良。
该病例进一步扩展了 COL9 相关 STL 的突变和表型谱，表现更为严重。
