Expanding the spectrum of CEP55-associated disease to viable phenotypes

Elizabeth S. Barrie, Eline Overwater, Mieke M. van Haelst, M. Mahdi Motazacker, Kristen V. Truxal, Erin Crist, Roya Mostafavi, Eniko K. Pivnick, Asim F. Choudhri, Tara Chandra Narumanchi, Valerie Castelluccio, Laurence E. Walsh, Cheryl Garganta, Julie M. Gastier-Foster

Research output: Contribution to journalArticle


Homozygosity for nonsense variants in CEP55 has been associated with a lethal condition characterized by multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH syndrome) also known as Meckel-like syndrome. Missense variants in CEP55 have not previously been reported in association with disease. Here we describe seven living individuals from five families with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all have a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings are homozygous for a consensus splice site variant near the end of the gene. These affected girls all have severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. Here we compare our seven patients with three previously reported families with a prenatal lethal phenotype (MARCH syndrome/Meckel-like syndrome) due to homozygous CEP55 nonsense variants. Our series suggests that individuals with compound heterozygosity for nonsense and missense variants in CEP55 have a different viable phenotype. We show that homozygosity for a splice variant near the end of the CEP55 gene is also compatible with life.

Original languageEnglish (US)
Pages (from-to)1201-1208
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number5
StatePublished - May 1 2020


  • CEP55
  • MARCH syndrome
  • Meckel-like syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Barrie, E. S., Overwater, E., van Haelst, M. M., Motazacker, M. M., Truxal, K. V., Crist, E., Mostafavi, R., Pivnick, E. K., Choudhri, A. F., Narumanchi, T. C., Castelluccio, V., Walsh, L. E., Garganta, C., & Gastier-Foster, J. M. (2020). Expanding the spectrum of CEP55-associated disease to viable phenotypes. American Journal of Medical Genetics, Part A, 182(5), 1201-1208. https://doi.org/10.1002/ajmg.a.61512