A novel homozygous ZNF469 variant causing brittle cornea syndrome is associated with corneal ectasias in heterozygous carriers

Aim To describe a family segregating a novel truncating ZNF469 homozygous mutation causing brittle cornea syndrome type 1 in a male patient and associated with corneal ectasia in his two heterozygous young children. Methods A 49-year-old affected male and his 12- and 8-year-old, apparently healthy,...

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Bibliographic Details
Published in:International ophthalmology 2023-03, Vol.43 (3), p.807-815
Main Authors: Arce-González, Rocío, Chacon-Camacho, Oscar Francisco, Ordoñez-Labastida, Vianey, Graue-Hernandez, Enrique O., Navas-Pérez, Alejandro, Zenteno, Juan Carlos
Format: Article
Language:English
Subjects:
Anomalies
Brittleness
Child
Child, Preschool
Children
Cornea
Corneal Topography
Deoxyribonucleic acid
Dilatation, Pathologic
DNA
DNA sequencing
Eye Abnormalities - diagnosis
Eye Abnormalities - genetics
Genetic analysis
Heterozygosity
Heterozygote
Humans
Keratoconus
Keratoconus - genetics
Male
Males
Medicine
Medicine & Public Health
Middle Aged
Ophthalmology
Original Paper
Siblings
Skin Abnormalities - diagnosis
Skin Abnormalities - genetics
Thickness measurement
Transcription Factors - genetics
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Summary:Aim To describe a family segregating a novel truncating ZNF469 homozygous mutation causing brittle cornea syndrome type 1 in a male patient and associated with corneal ectasia in his two heterozygous young children. Methods A 49-year-old affected male and his 12- and 8-year-old, apparently healthy, siblings underwent phenotypic and genetic assessment. An Oculus Pentacam Scheimpflug topographer system was employed for keratometries and central corneal thickness measurements. Exome sequencing was performed in DNA from the index case with subsequent Sanger sequencing confirmation of the ZNF469 gene causal variant in his relatives. Results The index case had a history of bilateral keratoglobus, corneal perforations, bilateral hypoacusia, and skeletal anomalies. His two children exhibited topographic anomalies compatible with keratoconus suspects as well as mild skeletal anomalies. Genetic analysis identified a novel homozygous c.2340delC variant in the ZNF469 gene, which predicts a p.(Arg781Glu fs *19) truncated protein. Sanger sequencing identified heterozygosity for the c.2340delC variant in DNA from both siblings. Conclusion Our results expand the mutational spectrum associated with brittle cornea syndrome and provide the first demonstration of early corneal anomalies in subjects carrying monoallelic ZNF469 variants.
ISSN:1573-2630
0165-5701
1573-2630
DOI:10.1007/s10792-022-02481-5