Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region.
Adolescent
Aged
Aged, 80 and over
Animals
Forkhead Transcription Factors
/ genetics
Genetic Linkage
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Nerve Tissue Proteins
/ genetics
Pedigree
Rett Syndrome
/ genetics
Sequence Deletion
Strabismus
/ genetics
Exome Sequencing
Whole Genome Sequencing
Young Adult
genetic linkage
genomics
high-throughput nucleotide sequencing
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
02
06
2020
revised:
05
09
2020
accepted:
29
09
2020
pubmed:
2
12
2020
medline:
9
3
2022
entrez:
1
12
2020
Statut:
ppublish
Résumé
Strabismus is a common condition, affecting 1%-4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is based on a seven-generation family with isolated strabismus inherited in an autosomal dominant manner. A total of 13 individuals from a common ancestor have been included for linkage analysis. Among these, nine are affected and four are unaffected. A single linkage signal has been identified at an 8.5 Mb region of chromosome 14q12 with a multipoint LOD (logarithm of the odds) score of 4.69. Disruption of this locus is known to cause FOXG1 syndrome (or congenital Rett syndrome; OMIM #613454 and *164874), in which 84% of affected individuals present with strabismus. With the incorporation of next-generation sequencing and in-depth bioinformatic analyses, a 4 bp non-coding deletion was prioritised as the top candidate for the observed strabismus phenotype. The deletion is predicted to disrupt regulation of
Identifiants
pubmed: 33257509
pii: jmedgenet-2020-107226
doi: 10.1136/jmedgenet-2020-107226
pmc: PMC8685624
doi:
Substances chimiques
FOXG1 protein, human
0
Forkhead Transcription Factors
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
46-55Subventions
Organisme : CIHR
ID : GSD-146285
Pays : Canada
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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