Exome sequencing in patients with microphthalmia, anophthalmia, and coloboma (MAC) from a consanguineous population.
Anophthalmos
/ genetics
Calcium-Binding Proteins
/ genetics
Cation Transport Proteins
/ genetics
Cell Adhesion Molecules
/ genetics
Coloboma
/ genetics
Consanguinity
Exome
/ genetics
Female
High-Throughput Nucleotide Sequencing
Humans
Kinesins
/ genetics
Male
Membrane Proteins
/ genetics
Microphthalmos
/ genetics
Mitochondrial Membrane Transport Proteins
/ genetics
Mutation
/ genetics
Nerve Tissue Proteins
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Tumor Suppressor Proteins
/ genetics
Exome Sequencing
Anophthalmia
CDON
Coloboma
Microphthalmia
TENM3
cataract
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:
14
05
2020
revised:
08
08
2020
accepted:
10
08
2020
pubmed:
18
8
2020
medline:
21
8
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
Next-generation sequencing strategies have resulted in mutation detection rates of 21% to 61% in small cohorts of patients with microphthalmia, anophthalmia and coloboma (MAC), but despite progress in identifying novel causative genes, many patients remain without a genetic diagnosis. We studied a cohort of 19 patients with MAC who were ascertained from a population with high rates of consanguinity. Using single nucleotide polymorphism (SNP) arrays and whole exome sequencing (WES), we identified one pathogenic variant in TENM3 in a patient with cataracts in addition to MAC. We also detected novel variants of unknown significance in genes that have previously been associated with MAC, including KIF26B, MICU1 and CDON, and identified variants in candidate genes for MAC from the Wnt signaling pathway, comprising LRP6, WNT2B and IQGAP1, but our findings do not prove causality. Plausible variants were not found for many of the cases, indicating that our current understanding of the pathogenesis of MAC, a highly heterogeneous group of ocular defects, remains incomplete.
Identifiants
pubmed: 32799327
doi: 10.1111/cge.13830
pmc: PMC8077035
mid: NIHMS1691065
doi:
Substances chimiques
CDON protein, human
0
Calcium-Binding Proteins
0
Cation Transport Proteins
0
Cell Adhesion Molecules
0
MICU1 protein, human
0
Membrane Proteins
0
Mitochondrial Membrane Transport Proteins
0
Nerve Tissue Proteins
0
TENM3 protein, human
0
Tumor Suppressor Proteins
0
KIF26B protein, human
EC 3.6.1.-
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-506Subventions
Organisme : NICHD NIH HHS
ID : P50 HD103538
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006542
Pays : United States
Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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