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Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function
- Source :
- American Journal of Medical Genetics Part A. :952-964
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- Schnyder crystalline corneal dystrophy (SCCD) is a rare autosomal dominant disease characterized by progressive corneal opacification resulting from abnormal deposition of cholesterol and phospholipids. Recently, six different mutations on the UBIAD1 gene on chromosome 1p36 were found to result in SCCD. The purpose of this article is to further characterize the mutation spectrum of SCCD and identify structural and functional consequences for UBIAD1 protein activity. DNA sequencing was performed on samples from 36 individuals from 14 SCCD families. One affected individual was African American and SCCD has not been previously reported in this ethnic group. We identified UBIAD1 mutations in all 14 families which had 30 affected and 6 unaffected individuals. Eight different UBIAD1 mutations, 5 novel (L121F, D118G, and S171P in exon 1, G186R and D236E in exon 2) were identified. In four families with DNA samples from both affected and unaffected individuals, the D118G, G186R, T175I, and G177R mutations cosegregated with SCCD. In combination with our previous report, we have identified the genetic mutation in UBIAD1 in 20 unrelated families with 10 (including 5 reported here), having the N102S mutation. The results suggest that N102S may be a mutation hot spot because the affected families were unrelated including Caucasian and Asian individuals. There was no genotype phenotype correlation except for the T175I mutation which demonstrated prominent diffuse corneal haze, typically without corneal crystals. Protein analysis revealed structural and functional implications of SCCD mutations which may affect UBIAD1 function, ligand binding and interaction with binding partners, like apo E.
- Subjects :
- Adult
Male
medicine.medical_specialty
Adolescent
DNA Mutational Analysis
Molecular Sequence Data
Corneal dystrophy
Biology
medicine.disease_cause
Genetic analysis
DNA sequencing
chemistry.chemical_compound
Exon
Apolipoproteins E
Genetics
medicine
Humans
Point Mutation
Family
Amino Acid Sequence
Child
Genetics (clinical)
Aged
Aged, 80 and over
Corneal Dystrophies, Hereditary
Mutation
Protein function
Autosomal dominant trait
Proteins
Middle Aged
Dimethylallyltranstransferase
medicine.disease
Pedigree
chemistry
Amino Acid Substitution
Schnyder crystalline corneal dystrophy
Medical genetics
Female
DNA
Protein Binding
Subjects
Details
- ISSN :
- 15524833 and 15524825
- Database :
- OpenAIRE
- Journal :
- American Journal of Medical Genetics Part A
- Accession number :
- edsair.doi.dedup.....afea986ed76a8ee6bf58f4e9216b88f2