Intrafamilial Phenotypic Heterogeneity in a Chinese Family with a <b><i>POLR1D</i></b> p.Q31Rfs*10 Variant: A Challenge in Prenatal Diagnosis

Abstract

<b><i>Introduction:</i></b> Treacher Collins syndrome (TCS), also known as mandibulofacial dysostosis, is an inherited craniofacial defect. Here, we report a TCS family in which the members carry the same <i>POLR1D</i> variant but present with phenotypic variability. <b><i>Case Presentation:</i></b> A 19-year-old healthy primigravida was revealed by ultrasound at 12 weeks of gestation to have a fetus with micrognathia. Prenatal genetic testing detected a heterozygous single-nucleotide deletion (NM_015972:c.91del, p.Q31Rfs*10) in the <i>POLR1D</i> gene, inherited from the healthy mother. Variants of <i>POLR1D</i> have been reported to be associated with TCS. Family studies found that a paternal healthy cousin of the mother had a similar pregnancy outcome, with a fetus of TCS and the same <i>POLR1D</i> variant. <b><i>Discussion:</i></b> Our study results pose a great challenge to prenatal diagnosis of TCS. The prenatal diagnosis cannot only rely on genetic testing. Instead, an early detailed sonographic survey will be helpful for the identification of TCS.