Compound heterozygous splicing CDON variants result in isolated ocular coloboma.
CDON
coloboma
dual diagnosis
recessive
splicing
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
24
06
2020
revised:
23
07
2020
accepted:
25
07
2020
pubmed:
31
7
2020
medline:
21
8
2021
entrez:
31
7
2020
Statut:
ppublish
Résumé
Ocular coloboma is caused by failure of optic fissure closure during development and recognized as part of the microphthalmia, anophthalmia, and coloboma (MAC) spectrum. While many genes are known to cause colobomatous microphthalmia, relatively few have been reported in coloboma with normal eye size. Genetic analysis including trio exome sequencing and Sanger sequencing was undertaken in a family with two siblings affected with bilateral coloboma of the iris, retina, and choroid. Pathogenic variants in MAC genes were excluded. Trio analysis identified compound heterozygous donor splice site variants in CDON, a cell-surface receptor known to function in the Sonic Hedgehog pathway, c.928 + 1G > A and c.2650 + 1G > T, in both affected individuals. Heterozygous missense and truncating CDON variants are associated with dominant holoprosencephaly (HPE) with incomplete penetrance and Cdon-/- mice display variable HPE and coloboma. A homozygous nonsense allele of uncertain significance was recently identified in a consanguineous patient with coloboma and a second molecular diagnosis. We report the first compound heterozygous variants in CDON as a cause of isolated coloboma. CDON is the first HPE gene identified to cause recessive coloboma. Given the phenotypic overlap, further examination of HPE genes in coloboma is indicated.
Identifiants
pubmed: 32729136
doi: 10.1111/cge.13824
pmc: PMC8341436
mid: NIHMS1728214
doi:
Substances chimiques
CDON protein, human
0
Cdon protein, mouse
0
Cell Adhesion Molecules
0
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
486-492Subventions
Organisme : Clinical and Translational Science Award (CTSI) program
ID : 1UL1RR031973
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : R21HD099701
Organisme : NEI NIH HHS
ID : R01 EY025718
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD099701
Pays : United States
Organisme : NEI NIH HHS
ID : R01EY025718
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR031973
Pays : United States
Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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