Characterization of ARB in twins: in-trans frameshift and deep intronic BEST1 variants.
Victor Lin, Eugene Yu-Chuan Kang, Laura Liu et al.
✦ AI-curated · Sources linked
Case in brief
Ten-year-old dizygotic twins presented with bilateral reduced visual acuity and characteristic retinal findings, including multifocal yellow-white flecks, subretinal hyperreflective material with interlaminar splitting, and mild subretinal or intraretinal fluid. Electro-oculography showed severely reduced Arden ratios, and full-field electroretinography showed subnormal rod and cone responses. Initial genetic testing identified a BEST1 frameshift; further analysis found a second, deep intronic variant in trans. Both twins carried the maternally inherited c.353_362dup frameshift and paternally inherited c.867+97G>A variant, consistent with autosomal recessive bestrophinopathy. Their asymptomatic parents were heterozygous carriers.
What made this case unusual
The second disease-associated BEST1 variant was deep intronic and was identified after the twins initially appeared to carry only one frameshift variant, illustrating how coding-focused testing may leave the molecular diagnosis incomplete.
Diagnostic / clinical pearl
When the phenotype supports autosomal recessive bestrophinopathy but testing finds only one BEST1 coding variant, consider targeted analysis of intronic regions to look for a second variant in trans.