A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes.
Sci Rep
; 7(1): 7799, 2017 08 10.
Article
in En
| MEDLINE
| ID: mdl-28798362
ABSTRACT
Congenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestations included bilateral excavated optic disc with multiple cilioretinal vessels emerging and bilateral retinoschisis with great variability in the range of extension and severity. Other intra-familial phenotypic diversities were also noted, including severity in retinal atrophy, onset age of visual impairment and presence of congenital nystagmus and strabismus. Genome-wide linkage analysis and fine mapping mapped a novel locus for CODA to a 34.3 cM interval between D14S972 and D14S139 at 14q12-q22.1. A maximum multi-point log odds score of 3.901 was reached at D14S275. However, no mutation was identified by exome sequencing or direct sequencing of PAX6 and PAX2 genes, suggesting that the mutation may reside within a regulatory element. In conclusion, we find retinoschisis as a necessary consequence of optic nerve head (ONH) anomalies. The complicated phenotype observed in the family provided additional insights into the inherited ONH anomalies. Mapping of a novel locus, 14q12-q22.1, implies a new disease-causing gene and potential distinct pathogenesis for CODA.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Optic Disk
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Chromosomes, Human, Pair 14
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Eye Diseases, Hereditary
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Chromosome Mapping
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Genetic Predisposition to Disease
Type of study:
Prognostic_studies
Limits:
Adult
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Sci Rep
Year:
2017
Document type:
Article
Affiliation country:
China
Country of publication:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM