Expanding the spectrum of CEP55-associated disease to viable phenotypes.
Abnormalities, Multiple
/ epidemiology
Adolescent
Adult
Cell Cycle Proteins
/ genetics
Cerebellum
/ abnormalities
Child
Child, Preschool
Dandy-Walker Syndrome
/ epidemiology
Developmental Disabilities
/ epidemiology
Female
Genetic Predisposition to Disease
Homozygote
Humans
Infant
Infant, Newborn
Male
Microcephaly
/ epidemiology
Mutation
Mutation, Missense
Nervous System Malformations
/ epidemiology
Pancreatic Cyst
/ epidemiology
Pedigree
Phenotype
Pregnancy
Young Adult
CEP55
MARCH syndrome
Meckel-like syndrome
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
22
07
2019
revised:
13
01
2020
accepted:
17
01
2020
pubmed:
27
2
2020
medline:
13
1
2021
entrez:
27
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32100459
doi: 10.1002/ajmg.a.61512
doi:
Substances chimiques
Cell Cycle Proteins
0
Cep55 protein, human
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
1201-1208Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
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