Abstract
Background: Poirier–Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of CSNK2B. Methods: Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of CSNK2B mutation. Results: We reported nine unrelated patients with heterozygous de novo mutations of the CSNK2B gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of CSNK2B that have not been reported previously. Conclusion: Although it was not possible to assess a genotype–phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene.
Highlights
Poirier–Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disorder associated with mutations involving the gene CSNK2B
All patients presented de novo mutations of CSNK2B, which were missense in four (44%) cases, frameshift and nonsense in two (22%) cases, and splicing in one (11%) case (Figure 1), as shown in Scheme 1
POBINDS is a PraOreBInNeuDrSodisevaerlaorpemneenutraolddeivsoerlodpemr reenlatatel dditsoolrodsesr-orfe-lfautnedctitoonlomssu-toaft-ifounnsction mu of CSNK2B. It wtioanssfiorfstCdSeNsKcr2iBb.eIdt wbyasPfoirirsitedreastcarilb. eind 2b0y1P7oiinritewr aotpaal.tienn2t0s1w7 iitnhtiwnotepllaetciteunatls with int disability and,lienctounael dciassaeb,imlityoacnlodn, inc eopnielecpasye,[m2]y. oItcslopnaictheopgileenpessyis[2a]p. pItesaprastthoobgensetsrisctalyppears to linked with dyssfturincctltyiolninskoefdkwiniathsedCyKsf2u,nachtieotnersootfetkrianmaseer CcoKn2s,taithuetetedrobtyetCrSamNKer2cBo,nCsStiNtuKt2eAd 1by CSNK2 and CSNK2A2CwShNicKh2Ais1inanvdolCveSdNKin2Ase2vwerhailcshigisnianlivnoglvpeadthinwsaeyvser[a5l,9s]i.gnaling pathways [5,9]
Summary
Poirier–Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disorder associated with mutations involving the gene CSNK2B. Current evidence suggests that POBINDS could manifest with a wide range of symptoms, including early-onset epilepsy, a variable degree of intellectual disability (ID), developmental disability (DD), and growth abnormalities [1,2,3] Such symptoms define a wide spectrum of phenotypes, ranging from well-controlled seizure and mild ID to intractable epilepsy, recurrent refractory status epilepticus (SE), and severe neurodevelopmental delay. This evidence allows us to presume that the different clinical pictures might be related to the diverse alterations involving the POBINDS gene. Conclusion: it was not possible to assess a genotype–phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call