A Recurrent Variant in POLR1B, c.3007C>T; p.Arg1003Cys, Associated with Atresia of the External Canal and Microtia in Treacher Collins Syndrome Type 4

Abstract

Treacher Collins syndrome (TCS) is a heterogenous malformation syndrome characterized by a distinct facial appearance including downslanting palpebral fissures, malar hypoplasia, conductive hearing loss, and mandibular hypoplasia. Recently, a new causative gene, <i>POLR1B</i>, encoding DNA-directed RNA polymerase I subunit RPA2, was identified as a fourth type of TCS (TCS4). We describe another patient with TCS4 caused by a recurrent <i>POLR1B</i> variant, c.3007C&#x3e;T; p.Arg1003Cys. Including our patient, all 4 patients with p.(Arg1003Cys) had atresia of the external auditory canal and microtia. All of the reported pathogenic variants in <i>POLR1B</i> were clustered at only 2 residues. Our patient highlights the genotype-phenotype correlation in TCS4 associated with <i>POLR1B</i>.