■评估LTBP2突变的频率,并详细阐述LTBP2相关的临床表型在中国先天性扁桃体外翻(CEL)队列。
■总共,本研究招募了145名具有CEL的中国先证者,并进行了眼部和全身检查。全外显子组测序用于鉴定突变,进一步进行Sanger测序和生物信息学分析以验证致病性突变。
■总的来说,LTBP2中涉及八个新突变的双等位基因突变(c.4370-7_4370-9delTCT,c.4370-5C>G,c.3452G>A,c.2253delG,c.4114T>C,c.1251G>A,c.4760G>A,和c.620G>A)在四个CEL先证中鉴定(4/145,2.76%)。LTBP2突变的患者以巨大角膜为特征,球眼,高度近视,青光眼而不是平坦的角膜,高角膜散光,在其他基因突变中报道的心血管和骨骼异常。检测到一种新的纯合移码突变,发现这种类型的突变比其他突变引起更复杂的眼部症状,从眼前节到眼底。
■本研究报告了中国CEL队列中LTBP2基因的突变频率,并提供了对CEL中LTBP2相关基因型-表型关联的新见解。
To evaluate the frequency of LTBP2 mutations and to elaborate on LTBP2-related clinical phenotypes in a Chinese congenital ectopia lentis (CEL) cohort.
In total, 145 Chinese probands with CEL were recruited for this study and underwent ocular and systemic examinations. Whole-exome sequencing was used to identify mutations, and Sanger sequencing and bioinformatics analysis were further performed to verify pathogenic mutations.
Overall, biallelic mutations in LTBP2 involving eight novel mutations (c.4370-7_4370-9delTCT, c.4370-5C>G, c.3452G>A, c.2253delG, c.4114T>C, c.1251G>A, c.4760G>A, and c.620G>A) were identified in four CEL probands (4/145, 2.76%). Patients with LTBP2 mutations were characterized by a megalocornea, spherophakia, high myopia, and glaucoma instead of a flat cornea, high corneal astigmatism, cardiovascular and skeletal abnormalities that were reported in other gene mutations. A novel homozygous frameshift mutation was detected, and this type of mutation was found to cause more complicated ocular symptoms than others, ranging from the anterior segment to the fundus.
This study reported the mutation frequency of the LTBP2 gene in a Chinese CEL cohort and provided novel insight into LTBP2-related genotype-phenotype associations in CEL.