PUBLICATION

Novel truncation mutations in MYRF cause autosomal dominant high hyperopia mapped to 11p12-q13.3

Authors
Xiao, X., Sun, W., Ouyang, J., Li, S., Jia, X., Tan, Z., Hejtmancik, J.F., Zhang, Q.
ID
ZDB-PUB-190608-8
Date
2019
Source
Human genetics   138(10): 1077-1090 (Journal)
Registered Authors
Hejtmancik, J. Fielding
Keywords
none
MeSH Terms
  • Pedigree
  • Membrane Proteins/genetics*
  • Lod Score
  • Transcription Factors/genetics*
  • Genetic Loci
  • Mutation*
  • Genetic Association Studies*
  • Chromosome Mapping
  • Female
  • Phenotype
  • Male
  • Chromosomes, Human, Pair 11*
  • Hyperopia/diagnosis
  • Hyperopia/genetics*
  • Eye Diseases, Hereditary/diagnosis
  • Eye Diseases, Hereditary/genetics*
  • Gene Knockout Techniques
  • Zebrafish
  • DNA Mutational Analysis
  • Fluorescein Angiography
  • Genes, Dominant*
  • Humans
  • Animals
  • Genetic Predisposition to Disease*
(all 24)
PubMed
31172260 Full text @ Hum. Genet.
Abstract
High hyperopia is a common and severe form of refractive error. Genetic factors play important roles in the development of high hyperopia but the exact gene responsible for this condition is mostly unknown. We identified a large Chinese family with autosomal dominant high hyperopia. A genome-wide linkage scan mapped the high hyperopia to chromosome 11p12-q13.3, with maximum log of the odds scores of 4.68 at theta = 0 for D11S987. Parallel whole-exome sequencing detected a novel c.3377delG (p.Gly1126Valfs*31) heterozygous mutation in the MYRF gene within the linkage interval. Whole-exome sequencing in other 121 probands with high hyperopia identified additional novel mutations in MYRF within two other families: a de novo c.3274_3275delAG (p.Leu1093Profs*22) heterozygous mutation and a c.3194+2T>C heterozygous mutation. All three mutations are located in the C-terminal region of MYRF and are predicted to result in truncation of that portion. Two patients from two of the three families developed angle-closure glaucoma. These three mutations were present in neither the ExAC database nor our in-house whole-exome sequencing data from 3280 individuals. No other truncation mutations in MYRF were detected in the 3280 individuals. Knockdown of myrf resulted in small eye size in zebrafish. These evidence all support that truncation mutations in the C-terminal region of MYRF are responsible for autosomal dominant high hyperopia in these families. Our results may provide useful clues for further understanding the functional role of the C-terminal region of this critical myelin regulatory factor, as well as the molecular pathogenesis of high hyperopia and its associated angle-closure glaucoma.
Genes / Markers
Figures
Figure Gallery (3 images)
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Expression
No data available
Phenotype
Fish Conditions Stage Phenotype Figure
AB + MO1-myrfstandard conditionsProtruding-mouth
AB + MO1-myrfstandard conditionsDay 5
AB + MO1-myrfstandard conditionsDay 5
AB + MO1-myrfstandard conditionsDay 5
AB + MO1-myrfstandard conditionsDay 5
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Mutations / Transgenics
No data available
Human Disease / Model
Human Disease Fish Conditions Evidence
angle-closure glaucomaTAS
eye diseaseAB + MO1-myrfstandard conditionsTAS
hyperopiaTAS
1 - 3 of 3
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Sequence Targeting Reagents
Target Reagent Reagent Type
myrfMO1-myrfMRPHLNO
1 - 1 of 1
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Fish
Fish
AB
AB + MO1-myrf
WT
1 - 3 of 3
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Antibodies
Name Type Antigen Genes Isotypes Host Organism
Ab1-elavlmonoclonalIgG2bMouse
Ab1-glulmonoclonal
    		IgG2aMouse
    Ab1-pax6polyclonal
      		IgGRabbit
      Ab1-prkcapolyclonalIgGRabbit
      Ab2-recoverinpolyclonal
        		Rabbit
        Ab3-rhomonoclonalIgG1Mouse
        1 - 6 of 6
        Show
        Orthology
        No data available
        Engineered Foreign Genes
        No data available
        Mapping
        No data available
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        Citation
        Xiao, X., Sun, W., Ouyang, J., Li, S., Jia, X., Tan, Z., Hejtmancik, J.F., Zhang, Q. (2019) Novel truncation mutations in MYRF cause autosomal dominant high hyperopia mapped to 11p12-q13.3. Human genetics. 138(10):1077-1090.