Mutations in FYCO1 identified in families with congenital cataracts.
Mol Vis
; 26: 334-344, 2020.
Article
in En
| MEDLINE
| ID: mdl-32355443
ABSTRACT
Purpose:
This study was designed to identify the pathogenic variants in three consanguineous families with congenital cataracts segregating as a recessive trait.Methods:
Consanguineous families with multiple individuals manifesting congenital cataracts were ascertained. All participating members underwent an ophthalmic examination. A small aliquot of the blood sample was collected from all participating individuals, and genomic DNAs were extracted. Homozygosity-based linkage analysis was performed using short tandem repeat (STR) markers. The haplotypes were constructed with alleles of the STR markers, and the two-point logarithm of odds (LOD) scores were calculated. The candidate gene was sequenced bidirectionally to identify the disease-causing mutations.Results:
Linkage analysis localized the disease interval to chromosome 3p in three families. Subsequently, bidirectional Sanger sequencing identified two novel mutations-a single base deletion resulting in a frameshift (c.3196delC; p.His1066IlefsTer10) mutation and a single base substitution resulting in a nonsense (c.4270C>T; p.Arg1424Ter) mutation-and a known missense (c.4127T>C, p.Leu1376Pro) mutation in FYCO1. All three mutations showed complete segregation with the disease phenotype and were absent in 96 ethnically matched control individuals.Conclusions:
We report two novel mutations and a previously reported mutation in FYCO1 in three large consanguineous families. Taken together, mutations in FYCO1 contribute nearly 15% to the total genetic load of autosomal recessive congenital cataracts in this cohort.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cataract
/
Microtubule-Associated Proteins
Type of study:
Prognostic_studies
Limits:
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Mol Vis
Journal subject:
BIOLOGIA MOLECULAR
/
OFTALMOLOGIA
Year:
2020
Type:
Article
Affiliation country:
Pakistan