Biallelic missense CEP55 variants cause prenatal MARCH syndrome.

Autor: Fu L; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.; Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan., Yamamoto Y; Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan., Seyama R; Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan., Matsuzawa N; Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan., Nagaoka M; Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan., Yao T; Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, Japan., Hamada K; Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Ogata K; Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Suzuki T; Department of Obstetrics and Gynecology, Keiai Hospital, Saitama, Japan., Tsuchida N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.; Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan., Uchiyama Y; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.; Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan., Koshimizu E; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Misawa K; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Miyatake S; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.; Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan., Mizuguchi T; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Fujita A; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Itakura A; Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan., Matsumoto N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. naomat@yokohama-cu.ac.jp.; Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan. naomat@yokohama-cu.ac.jp.; Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan. naomat@yokohama-cu.ac.jp.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2024 Oct 16. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1038/s10038-024-01298-7
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
Databáze: MEDLINE
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