A de novo PUF60 mutation in a child with a syndromic form of coloboma and persistent fetal vasculature

We performed whole exome sequencing (WES) in a patient with a clinical diagnosis of possible CHARGE syndrome, where CHD7 analysis and array CGH did not identify any pathogenic variant. The boy presented prenatal and postnatal growth retardation, bilateral coloboma, a complex heart defect, hemivertebrae, monolateral renal agenesis and dysmorphic features. WES analysis identified a de novo c.532G>A mutation leading to pGlu178Lys change in PUF60, a gene predicted to be involved in some of the clinical aspects of 8q24.3 microdeletion syndrome. In this regard, rare copy number variants (CNVs) encompassing PUF60 and a single de novo missense variant in this gene were previously described. Patients showed a similar phenotype and manipulation of zebrafish attributed to PUF60 haploinsufficiency a fraction of clinical features, while coloboma and kidney anomalies were thought to be caused by haploinsufficiency of the neighboring SCRIB gene. Our results indicate that mutations in PUF60 may be fully responsible of this clinical entity, which shows a significant overlap with CHARGE syndrome.