A Case of Okur-Chung Neurodevelopmental Syndrome with a Novel, de novo Variant on the CSNK2A1 Gene in a Turkish Patient

Abstract

Introduction: Okur-Chung neurodevelopmental syndrome (OCNDS; #617062) has been associated with heterozygous mutations in the CSNK2A1 gene (*115440) mapped on the chromosome's 20p13 region.

Case presentation: The analysis was performed on a 2-year-old patient who was admitted to our genetic diseases evaluation center by his family with a complaint of hypotonia. We detected a heterozygous NM_177559.3 (CSNK2A1):c.1139_1140dupGG (p.Met381GlyfsTer32) variant in the CSNK2A1 gene from a whole-exome sequence analysis.

Conclusion: The variant that we detected has not been reported in open-access databases to date, so it was evaluated as a novel likely pathogenic variant according to the ACMG-2015 criteria. No variant was detected upon segregation analysis of the patient's parents; therefore, the related variant was evaluated as de novo. In this study, we offer the first report of a pathogenic frameshift variant in the CSNK2A1 gene that has a relationship with OCNDS.

Keywords: De novo variant; Hypotonia; Neurodevelopmental syndrome; Novel; Whole-exome sequencing.

Fig. 1.

Clinical findings of our case with Okur-Churg syndrome. a The patient has a wide forehead, flattened, and wide nasal root. b Epicanthal folds in the right eye, long eyelashes, minimal ptosis, micrognathia. c Low-set simple ears. d Mild clinodactyly. e Overlapping was observed in the toe.

Fig. 2.

Anatomical evaluation of the brain via magnetic resonance in our case. a 3D isovolumetric T1W in the sagittal plane was taken after IV contrast injection with SWI sequences. b TSE T2W-T1A-Flair in the axial plane, T2A in the coronal plane. c DWI and TSE T1W sections in the axial plane. A slight volume loss in the deep white matter in the occipital lobe is detected (green arrow).

Fig. 3.

Schematic presentation of the CSNK2A1 gene reported pathogenic variants associated with Okur-Chung syndrome and schematic representation of mature CK2α protein. The protein domains and regions were designed using the UniProt database. CSNK2A1:c.1139_1140dupGG variant takes place in the 14th exon of the gene that causes a frameshift and predicts loss of the stop codon.

Fig. 4.

Sanger sequence family segregation results. The analysis of NM_177559.3 (CSNK2A1):c.1139_1140dupGG (p.Met381GlyfsTer32) variant is detected using the sanger sequencing method, the duplication of two Guanine nucleotides leads to a frameshift variation. We performed a trio analysis and we detected a de novo variant in our case that is not inherited from parents. The parents are homozygous wild type in this case.

Fig. 5.

Superimposition of the homology model (red) with the wild-type protein 6SPW (green).