背景：最佳卵黄样黄斑营养不良（BVMD），由BEST1基因的致病变异引起，尚未报道与白内障和眼部畸形有关。我们报道了一例复杂的眼部表型，包括小眼症，微角膜,白内障,卵黄样黄斑营养不良.
方法：一名6岁女孩表现出畏光和不良的视觉行为。彻底的眼科检查显示患者患有双侧小眼症，微角膜,先天性白内障,和最佳卵黄样黄斑营养不良（BVMD）。全外显子组测序(WES)鉴定了BEST1中的一个变体和CRYBB2基因中的一个变体:c.218T>Gp.(Ile73Arg)和c.479G>Cp.(Arg160Pro)。第一个变种是从先证者的父亲那里继承下来的,被诊断为亚临床BVMD,而第二个是从头变种。小基因分析表明，BEST1中c.218T>G不影响前mRNA剪接。
结论：本病例提示BVMD和先天性白内障伴小眼症的复杂眼部表型不能用一个基因的变异来解释，而是由BEST1和CRYBB2的变异引起。该病例强调了一般临床评估和综合基因检测对诊断复杂眼病的重要性。
BACKGROUND: Best vitelliform macular dystrophy (BVMD), caused by pathogenic variants of the BEST1 gene, has not been reported in association with cataracts and ocular malformations. We reported a
case with a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy.
METHODS: A six-year-old girl manifested photophobia and a poor visual behavior. A thorough ophthalmic examination revealed the patient to have bilateral microphthalmia, microcornea, congenital cataract, and Best vitelliform macular dystrophy (BVMD). Whole exome sequencing (WES) identified one variant in the BEST1 and one variant in CRYBB2 genes: c.218 T > G p.(Ile73Arg) and c.479G > C p.(Arg160Pro). The first variant was inherited from the proband\'s father, who was diagnosed with subclinical BVMD, while the second was a de novo variant. A minigene assay showed that c.218 T > G in BEST1 did not affect pre-mRNA splicing.
CONCLUSIONS: This
case suggests that the complex ocular phenotype comprising BVMD and congenital cataract with microphthalmia cannot be explained by variation in one gene but is caused by variants in BEST1 and CRYBB2. This
case highlights the importance of general clinical evaluation and comprehensive genetic testing for diagnosing complex eye diseases.
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