Novel Pathogenic Variant (c.1171A>T) in in a Female with Intellectual Disability and Craniofacial Anomalies.

Background: , along with and , is one of the causative genes of Potocki-Shaffer syndrome (PSS), a rare contiguous disorder involving chromosome region11p11.2. has been associated with intellectual developmental disorders and craniofacial anomalies and suggested as a candidate for more extended phenotypes. However, variants in and its associated phenotypes are yet to be fully explored, since reports on cases with variants affecting this gene are few worldwide. We present a novel heterogeneous variant in in a 26-year-old Korean female.

Methods: The patient's clinical manifestations were recorded and physical examination, cognitive assessment, brain imaging, metabolic screening, and cytogenetic testing including whole exome sequencing were pursued.

Results: Whole exome sequencing identified a de novo nonsense variant c.1171A>T (p.Lys391Ter), affecting the AT-hook domain. The patient showed an extended phenotypic spectrum along with intellectual developmental disorders and craniofacial anomalies, such as attention-deficit hyperactivity disorder, epilepsy, overgrowth, and hypotonia. Variants affecting the AT-hook domain are few in PSS, however, the phenotypic spectrum of the patient was in line with previously reported cases.

Conclusion: This case further reinforced and adds to the extended data on the phenotypes associated with haploinsufficiency.