Abstract
CEP55 encodes centrosomal protein 55 kDa, which plays a crucial role in mitosis, particularly cytokinesis. Biallelic CEP55 variants cause MARCH syndrome (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly). Here, we describe a Japanese family with two affected siblings harboring novel compound heterozygous CEP55 variants, NM_001127182: c.[1357 C > T];[1358 G > A] p.[(Arg453Cys)];[(Arg453His)]. Both presented clinically with typical lethal MARCH syndrome. Although a combination of missense and nonsense variants has been reported previously, this is the first report of biallelic missense CEP55 variants. These variants biallelically affected the same amino acid, Arg453, in the last 40 amino acids of CEP55. These residues are functionally important for CEP55 localization to the midbody during cell division, and may be associated with severe clinical outcomes. More cases of pathogenic CEP55 variants are needed to establish the genotype–phenotype correlation.
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Data availability
The relevant genomic data have not been deposited to public databases, but are available on request to the corresponding author.
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Acknowledgements
We express our gratitude to the family for their involvement in this research. We further acknowledge the great technical help provided by Mr. Takafumi Miyama, Ms. Sayaka Sugimoto, Ms. Mai Sato, Ms. Nobuko Watanabe, and Ms. Kaori Takabe at the Department of Human Genetics at Yokohama City University Graduate School of Medicine. The Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research [grant numbers JP22K15901 (A. Fujita), JP23H02829 (S. Miyatake), JP23H02877 (T. Mizuguchi), JP23K07229 (Y. Uchiyama), JP23K15353 (N. Tsuchida), and JP24K02230 (N. Matsumoto); the Takeda Science Foundation (T. Mizuguchi and N. Matsumoto)] and the Japan Agency for Medical Research and Development (AMED) under grant numbers JP23ek0109674, JP23ek0109549, and JP23ek0109617 (N. Matsumoto); and Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics (S. Miyatake) provided support for this work. We thank Catherine Perfect, MA (Cantab), and Susan Furness, PhD, from Edanz (https://jp.edanz.com/ac), for editing drafts of this manuscript.
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Fu, L., Yamamoto, Y., Seyama, R. et al. Biallelic missense CEP55 variants cause prenatal MARCH syndrome. J Hum Genet 70, 63–66 (2025). https://doi.org/10.1038/s10038-024-01298-7
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DOI: https://doi.org/10.1038/s10038-024-01298-7
