Novel Variants of CEP152 in a Case of Compound-Heterozygous Inheritance of Epilepsy

Abstract

Introduction CEP152 encodes protein Cep152, which associates with centrosome function. The lack of Cep152 can cause centrosome duplication to fail. CEP152 mutates, causing several diseases such as Seckel syndrome-5 and primary microencephaly-9.

Methods In this study, we reported a patient diagnosed with epilepsy in Tianjin Children's Hospital. We performed clinical examination and laboratory test, and whole-exome sequencing was performed for the proband's and his parents' peripheral blood. The suspected compound-heterozygous variant in the CEP152 gene was verified by Sanger sequencing and quantitative real-time polymerase chain reaction technology.

Results We discovered three variants—two of them from CEP152 and one from HPD. The result showed the variants in CEP152 only. The patient presented with seizures frequently. Sanger sequencing showed two novel variants in CEP152 are in exon26 (NM_014985.3 c.3968C > A p.Ser1323*) and in exon16 (NM_014985.3 c.2034_2036del p.Tyr678*).

Conclusions We reported a novel compound-heterozygous variant in the CEP152 gene in this study. Most of the phenotypes are Seckel syndrome and primary microencephaly, and the novel variant may cause an atypical phenotype that is epilepsy.

Keywords

CEP152 - compound-heterozygous - variants - phenotypes - WES - Sanger sequencing

Ethics Approval

After giving full authorization and signing a written informed consent by both parents, WES was performed. The ethics committee approved the study of Tianjin Children's Hospital (Tianjin, China).

Consent to Participate

Written informed consent was obtained from the parents.

Authors' Contributions

W.L. was involved in writing—original draft and visualization. X.L. and Jia Fu helped in writing—review and editing and resources. J.S. contributed to methodology. Y.Y. did formal analysis. D.L. conceptualized the study. C.C. helped in supervision, project administration, and funding acquisition.

^* Weiran Li and Xiaowei Lu contributed equally to this work.

Publikationsverlauf

Artikel online veröffentlicht:
16. Januar 2024

• References

• 1 Firat-Karalar EN, Rauniyar N, Yates III JR, Stearns T. Proximity interactions among centrosome components identify regulators of centriole duplication. Curr Biol 2014; 24 (06) 664-670
• 2 Wei Z, Kim TS, Ahn JI. et al. Requirement of the Cep57-Cep63 interaction for proper Cep152 recruitment and centriole duplication. Mol Cell Biol 2020; 40 (10) e00535-19
• 3 Kim TS, Park JE, Shukla A. et al. Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152. Proc Natl Acad Sci U S A 2013; 110 (50) E4849-E4857
• 4 Sonnen KF, Gabryjonczyk AM, Anselm E, Stierhof YD, Nigg EA. Human Cep192 and Cep152 cooperate in Plk4 recruitment and centriole duplication. J Cell Sci 2013; 126 (Pt 14): 3223-3233
• 5 Andersen JS, Wilkinson CJ, Mayor T, Mortensen P, Nigg EA, Mann M. Proteomic characterization of the human centrosome by protein correlation profiling. Nature 2003; 426 (6966) 570-574
• 6 Cizmecioglu O, Arnold M, Bahtz R. et al. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol 2010; 191 (04) 731-739
• 7 Kim TS, Zhang L, Il Ahn J. et al. Molecular architecture of a cylindrical self-assembly at human centrosomes. Nat Commun 2019; 10 (01) 1151
• 8 Dzhindzhev NS, Yu QD, Weiskopf K. et al. Asterless is a scaffold for the onset of centriole assembly. Nature 2010; 467 (7316) 714-718
• 9 Hatch EM, Kulukian A, Holland AJ, Cleveland DW, Stearns T. Cep152 interacts with Plk4 and is required for centriole duplication. J Cell Biol 2010; 191 (04) 721-729
• 10 Kalay E, Yigit G, Aslan Y. et al. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet 2011; 43 (01) 23-26
• 11 Shanske A, Caride DG, Menasse-Palmer L, Bogdanow A, Marion RW. Central nervous system anomalies in Seckel syndrome: report of a new family and review of the literature. Am J Med Genet 1997; 70 (02) 155-158
• 12 Børglum AD, Balslev T, Haagerup A. et al. A new locus for Seckel syndrome on chromosome 18p11.31-q11.2. Eur J Hum Genet 2001; 9 (10) 753-757
• 13 Woods CG, Bond J, Enard W. Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet 2005; 76 (05) 717-728
• 14 Faheem M, Naseer MI, Rasool M. et al. Molecular genetics of human primary microcephaly: an overview. BMC Med Genomics 2015; 8 :(Suppl 1, Suppl 1) S4
• 15 Xiong HY, Alipanahi B, Lee LJ. et al. RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science 2015; 347 (6218) 1254806
• 16 Software for assessing growth and development of the world's children. Version WHO Anthro for personal computers, version 3.2.2, 2011. Accessed December 6, 2023 at: http://www.who.int/childgrowth/software/en/ 2010
• 17 D'Alessandro LC, Al Turki S, Manickaraj AK. et al. Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect. Genet Med 2016; 18 (02) 189-198
• 18 Deng J, Weng X, Ye J, Zhou D, Liu Y, Zhao K. Identification of the germline mutation profile in esophageal squamous cell carcinoma by whole exome sequencing. Front Genet 2019; 10: 47
• 19 Kasak L, Hunter JM, Udani R. et al. CAGI SickKids challenges: assessment of phenotype and variant predictions derived from clinical and genomic data of children with undiagnosed diseases. Hum Mutat 2019; 40 (09) 1373-1391