Expanding the spectrum of CEP55‐associated disease to viable phenotypes. Issue 5 (25th February 2020)

• Record Type: Journal Article
• Authors: Barrie, Elizabeth S.; Overwater, Eline; van Haelst, Mieke M.; Motazacker, M. Mahdi; Truxal, Kristen V.; Crist, Erin; Mostafavi, Roya; Pivnick, Eniko K.; Choudhri, Asim F.; Narumanchi, TaraChandra; Castelluccio, Valerie; Walsh, Laurence E.; Garganta, Cheryl; Gastier‐Foster, Julie M.
• Is Part Of: American journal of medical genetics. Volume 182:Issue 5(2020)
• Page Start: 1201
• Page End: 1208
• Publication Date: 2020-02-25
• Subjects: CEP55 -- MARCH syndrome -- Meckel‐like syndrome; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61512
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: 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.