目的: 对1例先天性眼外肌纤维化患儿的TUBB3基因突变进行分析,寻找其病因。方法: 对患儿进行高分辨率高通量的全基因组芯片CNV分析及医学全外显子基因检测,并行Sanger测序验证。结果: 未发现疾病相关CNV区域。医学全外显子基因检测出患儿TUBB3基因的c.904G>T(p.Ala302Ser)杂合突变,该突变点在HGMD数据库未见报道,ACMG指南将其判定为致病性变异。Sanger测序验证结果显示患儿父母双方均未检出该变异。结论: TUBB3基因c.904G>T(p.Ala302Ser)杂合突变可能是该患儿的致病原因。

[1] RECK A C,MANNERS R,HATCHWELL E.Phenotypic heterogeneity may occur in congenital fibrosis of the extraocular muscles[J].Br J Ophthalmol,1998,82(6):676-679.
[2] PRICE J M,RANJODH S B,WASSERMAN B N.Congenital fibrosis of the extraocular muscles:review of recent literature[J].Curr Opin Ophthalmol,2019,30(5):314-318.
[3] 张俊涛,周炼红,查云飞,等.先天性眼外肌纤维化伴胼胝体发育不良一家系基因突变筛查[J].中华眼科杂志,2013,49(7):621-626.
[4] 杨璐,杨海军,易敬林,等.两个中国籍先天性眼外肌纤维化家系基因定位与临床分型[J].眼科新进展,2017,37(12):1153-1157.
[5] RICHARDS S,AZIZ N,BALE S,et al.Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology[J].Genet Med,2015,17(5):405-424.
[6] XUE J,SONG Z F,MA S Y,et al.A novel de novo TUBB3 variant causing developmental delay,epilepsy and mild ophthalmological symptoms in a Chinese child[J].J Mol Neurosci,2022,72(1):1-8.
[7] WHITMAN M C,ENGLE E C.Ocular congenital cranial dysinnervation disorders(CCDDs):insights into axon growth and guidance[J].Hum Mol Genet,2017,26(R1):R37-R44.
[8] MINOURA I,TAKAZAKI H,AYUKAWA R,et al.Reversal of axonal growth defects in an extraocular fibrosis model by engineering the kinesin-microtubule interface[J].Nat Commun,2016,7:10058.
[9] DENTICI M L,MAGLIONE V,AGOLINI E,et al.TUBB3 E410K syndrome:case report and review of the clinical spectrum of TUBB3 mutations[J].Am J Med Genet A,2020,182(8):1-8.
[10] POIRIER K,SAILLOUR Y,BAHU-BUISSON N,et al.Mutations in the neuronal ß-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects[J].Hum Mol Genet,2010,19(22):4462-4473.