Further delineation of the phenotype and genotype in a newly identified PAN2-related disorder.

Regulation of mRNA decay is a critical mechanism for effective gene expression. Poly(A) tail length is directly associated with mRNA stability, and deadenylation, which shortens poly(A) tails, plays a central role in mRNA regulation. PAN2 encodes a key component of the deadenylation machinery. Recently, loss-of-function variants in PAN2 have been associated with neurodevelopmental delay and multiple congenital anomalies in seven patients from five unrelated families. Here, we report two siblings presenting with neurodevelopmental delay and multiple congenital anomalies consistent with previously described PAN2-related cases. Notably, both siblings also exhibited esophageal atresia (EA) and developmental dysplasia of the hip (DDH). Whole-exome sequencing (WES) in the older sibling identified a novel homozygous nonsense variant in PAN2, c.1432C>T (p.Arg478Ter). Segregation analysis confirmed homozygosity in the affected sibling, remaining family members were carrier. This study expands the genotypic spectrum of PAN2-related disorder and suggests additional clinical features contributing to this newly emerging disorder.