Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610000, Sichuan Province, China.
Affiliated Hospital of Southwest Medical University, No.25, Taiping Street, Jiangyang District, Luzhou, 646000, Sichuan Province, China.
BMC Med Genomics. 2021 Sep 17;14(1):227. doi: 10.1186/s12920-021-01080-0.
Microspherophakia (MSP, OMIM 251,750) is a rare inherited autosomal recessive eye disorder characterized by small spherically shaped lens. Several studies have indicated that the transforming growth factor-beta (TGF-beta) binding proteins(LTBP2) gene mutation is the predominant cause of MSP. In our study, novel compound heterozygous mutations in the LTBP2 gene associated with MSP were reported, which was different from previous reported homozygous mutations.
The proband was an 18-year-old male in Western China with bilateral MSP, accompanied by ectopia lentis, secondary glaucoma and blindness in both eyes. In our hospital, he received bilateral lens resection and trabeculectomy combined with peripheral iridotomy. Using next-generation sequencing (NGS)-based gene panel tests, we identified pathogenic mutations in the peripheral blood DNA sample from the proband: c.3614_3618dupCTGGC (exon24, NM_000428) and c.2819G > A (exon18, NM_000428). The presence of the novel compound heterozygous mutations in the LTBP2 gene was linked with the development of MSP. Sanger sequencing confirmed the existence of one of the two variants in each parent respectively.
Our results demonstrated a rare case of MSP phenotype associated with novel compound heterozygous mutations in the LTBP2 gene using NGS technology.
小眼球症（MSP，OMIM 251,750）是一种罕见的常染色体隐性遗传性眼部疾病，其特征为眼球晶状体呈球形且体积较小。多项研究表明转化生长因子-β（TGF-β）结合蛋白（LTBP2）基因突变是 MSP 的主要原因。在我们的研究中，报告了与 MSP 相关的 LTBP2 基因新型复合杂合突变，与之前报道的纯合突变不同。
该先证者是一名 18 岁的中国西部男性，患有双侧 MSP，伴有晶状体异位、继发性青光眼和双眼失明。在我院，他接受了双眼晶状体切除术和小梁切除术联合周边虹膜切除术。使用基于下一代测序（NGS）的基因panel 测试，我们在该先证者外周血 DNA 样本中鉴定出致病性突变：c.3614_3618dupCTGGC（exon24，NM_000428）和 c.2819G > A（exon18，NM_000428）。LTBP2 基因的新型复合杂合突变的存在与 MSP 的发生有关。Sanger 测序分别证实了每个父母中存在两种变体中的一种。
我们的研究结果利用 NGS 技术，展示了一例罕见的 MSP 表型与 LTBP2 基因新型复合杂合突变相关。
