Whole-Exome Sequencing Identifies Novel Compound Heterozygous ZNF469 Mutations in Two Siblings with Mild Brittle Cornea Syndrome
Open Access
- 15 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Calcified Tissue International
- Vol. 107 (3), 294-299
- https://doi.org/10.1007/s00223-020-00721-3
Abstract
Connective tissue diseases, including osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS), exhibit a high degree of clinical and genetic heterogeneity. We report two sisters with blue sclerae, joint hypermobility and hearing loss. Whole-exome sequencing identified two compound heterozygous ZNF469 loss-of-function mutations due to a frameshift. Since these findings indicate the presence of brittle cornea syndrome (BCS), we performed ocular optical coherence tomography (OCT) and pachymetry, which revealed a moderate decrease in corneal thickness. While only one traumatic fracture was observed in each of the patients, a detailed skeletal assessment indicated no specific patterns of bone mass and microstructure reduction as well as normal bone turnover markers. Taken together, our findings point to a mild form of brittle cornea syndrome with a phenotype compatible with the extraskeletal features of OI but also with EDS.Keywords
Funding Information
- Bundesministerium für Bildung und Forschung (DIMEOs)
This publication has 22 references indexed in Scilit:
- Brittle cornea syndrome: current perspectivesClinical Ophthalmology, 2019
- MutationDistiller: user-driven identification of pathogenic DNA variantsNucleic Acids Research, 2019
- Zinc-finger proteins in health and diseaseCell Death Discovery, 2017
- Osteogenesis imperfectaThe Lancet, 2015
- Helical mutations in type I collagen that affect the processing of the amino-propeptide result in an Osteogenesis Imperfecta/Ehlers-Danlos Syndrome overlap syndromeOrphanet Journal of Rare Diseases, 2013
- GeneTalk: an expert exchange platform for assessing rare sequence variants in personal genomesBioinformatics, 2012
- Mutations in PRDM5 in Brittle Cornea Syndrome Identify a Pathway Regulating Extracellular Matrix Development and MaintenanceAmerican Journal of Human Genetics, 2011
- Brittle Cornea Syndrome Associated with a Missense Mutation in the Zinc-Finger 469 GeneInvestigative Ophthalmology & Visual Science, 2010
- Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea SyndromeAmerican Journal of Human Genetics, 2008
- Mutations Near Amino End of α1(I) Collagen Cause Combined Osteogenesis Imperfecta/Ehlers-Danlos Syndrome by Interference with N-propeptide ProcessingOnline Journal of Public Health Informatics, 2005