Background: Verheij syndrome (VRJS) is a rare microdeletion syndrome of chromosome 8q24.3 that is characterized by severe growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, psychomotor retardation, cardiac and renal defects, and dysmorphic facial features. Pathogenic variants of PUF60 (Poly-U Binding Splicing Factor 60 kDa) have been found to cause VRJS. Here we present a Turkish patient with Verheij syndrome who has typical facial dysmorphic features and renal and cardiac abnormalities, scoliosis, tethered cord, and mild intellectual disability.
Methods: This is a case report of a 11-year-old female child who presented with Verheij syndrome. Blood samples were collected from the patient and the family. We performed whole exome sequencing was used to identify potential genetic mutations. We also used 3-dimensional protein structure analysis to identify the effect of the mutation.
Results: A de-novo in-frame variant (c.449_457delCAAAGGGGG; p.Ala150_Phe152del) of the PUF60 gene was identified by whole exome sequencing. According to ACMG guidelines in 2015, the mutation is classified as pathogenic and it has been reported in the clinvar database. Results of in-silico prediction software tools predicted the mutation was pathogenic. Protein structure analysis showed that the three residues affected by the in-frame deletion form could lead to impaired stability and function of the PUF60 protein.
Conclusions: To date, 25 patients have been reported with PUF60 mutations in the medical literature. In this article, we report a patient with VRJS who had the unusual findings of tethered cord syndrome and renal abnormalities. As far as we know, this is the first patient from Turkey who has been diagnosed with Verheij syndrome.
Keywords: Coloboma; PUF60 gene; Verheij syndrome; rare genotype; tethered cord syndrome.