The gene PUF60 is located on 8q24.3. encodes a nucleic acid-binding protein that plays a role in a variety of nuclear processes, including pre-mRNA splicing and transcriptional regulation. Heterozygous variants in PUF60 cause a multisystem disorder characterized by a neurodevelopmental disorder with variable features of skeletal, cardiac, renal, and ophthalmologic features.
Verheij et al. (2009) reported two unrelated Dutch children born with overlapping congenital anomalies associated with large heterozygous de novo deletions of chromosome 8q24. Dauber et al. (2013) reported a clinical collective with overlaps, in which exome sequencing in one patient revealed a heterozygous de novo missense mutation in PUF60 as a primary driver for parts of the phenotype. The disease had been termed ‘Verheij syndrome’, yet due to its incoherent and highly variable phenotype from individuals with large gene deletions, is now being referred to as PUF60-associated multisystem disorder.
Diagnostic testing is usually performed via multi-gene panel and exome / genome sequencing, or in rare instances single-gene testing.
PUF60