Department of Ophthalmology, Universidade Federal de São Paulo, Sao Paulo 04039-032, Brazil.
Instituto Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil.
Genes (Basel). 2021 Jul 13;12(7):1069. doi: 10.3390/genes12071069.
Up to 25% of pediatric cataract cases are inherited, with half of the known mutant genes belonging to the crystallin family. Within these, crystallin beta B3 () has the smallest number of reported variants. Clinical ophthalmological and genetic-dysmorphological evaluation were performed in three autosomal dominant family members with pediatric cataract and microphthalmia, as well as one unaffected family member. Peripheral blood was collected from all participating family members and next-generation sequencing was performed. Bioinformatics analysis revealed a novel missense variant c.467G>A/p.Gly156Glu in in all family members with childhood cataract. This variant is classified as likely pathogenic by ACMG, and no previous descriptions of it were found in ClinVar, HGMD or Cat-Map. The only other mutation previously described in the fifth exon of is a missense variant that causes a change in amino acid from the same 156th amino acid to arginine and has been associated with pediatric cataract and microphthalmia. To the best of our knowledge, this is the first time the c.467G>A/p.Gly156Glu variant is reported and the second time a mutation in CRYBB3 has been associated with microphthalmia.
多达 25%的儿童白内障病例是遗传性的，其中一半已知的突变基因属于晶状体蛋白家族。在这些基因中，晶状体蛋白β B3 () 报告的变体数量最少。对 3 名患有儿童白内障和小眼球症的常染色体显性家族成员以及 1 名未受影响的家族成员进行了临床眼科和遗传发育畸形评估。从所有参与的家族成员中采集外周血，并进行下一代测序。生物信息学分析显示，所有患有儿童白内障的家族成员中都存在 第 467 位密码子 G>A/p.Gly156Glu 的新型错义变异。该变异被 ACMG 归类为可能致病，在 ClinVar、HGMD 或 Cat-Map 中均未发现先前的描述。第五外显子中先前描述的唯一其他突变是导致相同第 156 位氨基酸发生变化的错义变异，该变异与儿童白内障和小眼球症有关。据我们所知，这是首次报道 c.467G>A/p.Gly156Glu 变异，也是 CRYBB3 突变与小眼球症相关的第二次报道。
