A Case of Okur-Chung Neurodevelopmental Syndrome with a Novel, de novo Variant on the <i>CSNK2A1</i> 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.

Inherited loss of function variant in CSNK2A1: the oldest reported cases of Okur–Chung syndrome in a single family

“…A two-year-old patient had a milder phenotype of OCNDS with a de novo heterozygous frameshift variant NM_177559.3 (CSNK2A1): c.1139_1140dupGG (p. Met381GlyfsTer32). This resulted in an elongated C terminal with 29 different amino acids in the 3′ untranslated region that is also expected to lead to mRNA degradation (Drenushe et al ., 2024).…”

“…MRI often reveals cortical neuronal migration defects. Published variants to date include 27 missense, 1 loss of start codon leading to loss of the first 137 amino acids in N terminal, 2 nonsense variants, 1 frameshift variant and 2 splice site variants (Okur et al ., 2016; Trinh et al ., 2017; Akahira-Azuma et al ., 2018; Chiu et al ., 2018; Colavito et al ., 2018; Owen et al ., 2018; Duan et al ., 2019; Nakashima et al ., 2019; Martinez-Monseny et al ., 2020; Wu et al ., 2020, 2021; Xu et al ., 2020a, b; Ranganath et al ., 2021; Jafari Khamirani et al ., 2022; Murakami et al ., 2022; Belnap et al ., 2023; Drenushe et al ., 2024; Wafik et al ., 2023). Clinvar and DECIPHER, however, list 25 and 3 loss of function variants, respectively including nonsense, frameshift and splice site variants.…”