Whole-Exome Sequencing Identifies Novel Compound Heterozygous ZNF469 Mutations in Two Siblings with Mild Brittle Cornea Syndrome.

Calcified Tissue International
Tim RolvienRalf Oheim

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.

References

Sep 1, 1973·Annals of the Rheumatic Diseases·P BeightonC L Soskolne
May 3, 2008·American Journal of Human Genetics·Almogit AbuElon Pras
Aug 4, 2009·Nature Genetics·Bruno ReversadeUwe Kornak
Aug 8, 2009·Investigative Ophthalmology & Visual Science·Anne E ChristensenHelge Boman
Aug 3, 2010·Nature Methods·Jana Marie SchwarzDominik Seelow
Jun 15, 2011·American Journal of Human Genetics·Emma M M Burkitt WrightGraeme C M Black
May 7, 2013·Orphanet Journal of Rare Diseases·Emma M M Burkitt WrightGraeme C M Black
Sep 17, 2015·American Journal of Medical Genetics. Part a·Andreas R JaneckeBeat Steinmann
Nov 7, 2015·Lancet·Antonella Forlino, Joan C Marini
Feb 6, 2016·American Journal of Human Genetics·Giuseppina DivisatoFernando Gianfrancesco
May 19, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lauren A BurtSteven K Boyd
Mar 18, 2017·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Fransiska MalfaitBrad Tinkle
Apr 9, 2017·Calcified Tissue International·Xuan QiWeibo Xia
Nov 21, 2017·Cell Death Discovery·Matteo CassandriGiuseppe Raschellà
May 21, 2019·Nucleic Acids Research·Daniela HombachDominik Seelow
Sep 10, 2019·Clinical Ophthalmology·Andrew WalkdenLeon Au

❮ Previous
Next ❯

Citations

Aug 10, 2021·Disease Models & Mechanisms·Chloe M StantonVeronique Vitart

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
X-ray

Software Mentioned

MutationTaster
Integrated Genome Viewer
GeneTalk
MutationDistiller

Related Concepts

Related Feeds

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.