Identification of a New Variant of PUF60 Gene: Case Presentation and Literature Review.

Background/Aim: The aim of the study was to report the case of a 5-month-old boy with a complex prenatal and neonatal symptomatology diagnosed with a "de novo" pathogenic variant of PUF60 gene. Case Report: Our hospital, undertook the antenatal and postnatal care of a 27-year-old pregnant lady. This was her second baby with a previously healthy boy. During her routine first-trimester anomaly scan, increased nuchal translucency was noticed. Multiple anomalies were seen throughout her subsequent antenatal visits. This triggered a sequence of tests, examinations and differential diagnosis. The final diagnosis was made at 5 months postpartum following the result of the whole exome sequence, which described a variant of unknown clinical significance (VUS, class 3 variant) in the PUF60 gene. We are mindful that changing the classification of a variant of unknown significance is challenging and requires supporting and robust criteria. Considering clinical symptomatology produced by the pathogenic mutation in the PUF gene, the identified c.1640A>G variant may be categorized as likely pathogenic. Conclusion: Our case adds new insights on the pathology and the underlying process involved in the PUF60 variant spectrum disorders. It also highlights the limits of current prenatal tests.