Building upon success following release of the first patient registry for isolated hearing impairment due to otoferlin-related hearing impairment in late 2023, we are pleased to announce the addition of a second registry for patients with CABP2 (DFNB93) diagnoses. This dedicated database is a collaborative effort between the Institute of Human Genetics and Institute for Auditory Neuroscience at the University Medical Center Göttingen (UMG). The study aims to achieve deeper insights into the phenotype of patients, which, generally remains limited to sensorineural hearing loss. However, analysis of the mechanism in animal models suggests that the underlying mechanism may be more accurately characterized as auditory synaptopathy. This study also hopes to contribute to the development of new therapeutic approaches.

Adults, children, or minors (with parental consent), who have received a CABP2 genetic diagnosis are welcome to register. Participants can provide details on their medical history, progression of hearing impairment, treatment and genetic data. All data will be stored in pseudonymised form in compliance with the European General Data Protection Regulation (GDPR) for research purposes.

The registry aims to empower patient-driven science on a gene that has been a focus of research at the Göttingen campus for many years. To learn more about the registry, please follow this link:

The registry study has received ethical approved from the Ethics Committee of the University Medical Center Göttingen.

Contact: PD Dr. Barbara Vona, barbara.vona@med.uni-goettingen.de

Patients diagnosed with hearing loss due to variants in the otoferlin gene, or OTOF, can now participate in a specific registry at the University Medical Center Göttingen (UMG). The registry, which is administrated in a collaboration by the Institute of Human Genetics and the Institute of Auditory Neuroscience, connects patients with scientists that are experts in the research into various forms of hearing loss, their genetic basis and potential new approaches for their treatment.

The database is open to affected adults and children/adolescents (with their parents‘ consent). Information will be collected on the participant’s medical history, the natural history of the hearing impairment, the treatment, and relevant genetic data of the affected person. Data will be pseudonymized, processed and stored in accordance with the European General Data Protection Regulation. The study is led by PD Dr. Barbara Vona and aims at providing new insights into the mechanisms leading to this specific form of hearing loss and contributing to the development of new therapeutic approaches. Participants may choose to be contacted in the future to receive information about available clinical studies and therapeutic options at the UMG.

Hearing impairment belongs to the most common congenital conditions. Most cases of congenital hearing loss are due to genetic defects, and thousands of variants in hundreds of genes have been found to be responsible for hearing loss. One of these genes is OTOF. It contains the genetic information to produce otoferlin, a protein contained in the auditory sensory cells of the inner ear and is essential for transmitting acoustic signals from the inner hair cells to the auditory nerve cells.

Patients who wish to participate in the registry are invited to download an information leaflet from a specific registry website. Using a secured online system, they can then complete a consent form and a questionnaire. If they wish they can also upload clinical documentation like hearing test and genetic test findings.

The registry study has been approved by the Ethics Committee of the University Medical Center Göttingen.

Contact: PD Dr. Barbara Vona, barbara.vona@med.uni-goettingen.de

Congenital rare skeletal disorders are conditions that affect the development and growth of bone and cartilage tissue. In most cases they are genetic in nature. They manifest either as skeletal malformations alone or as characteristic combinations of symptoms that can also involve other tissues. In a collaboration led by Professor Uwe Kornak at the Institute of Human Genetics Göttingen, research teams from Germany, Austria, the Netherlands, Saudi Arabia, and the U.S. have discovered the genetic cause of a previously undescribed specific skeletal disorder. In their study, they identified homozygous variants in the AXIN1 gene in seven patients ranging in age from three months to 15 years old. Radiologically and clinically, these patients presented with a phenotype characterized by generally elevated bone mineral density, excessive skull bone tissue, abnormally large head size (macrocephaly), hip joint malformation, and a developmental delay of variable degree.

The researchers performed additional investigations in different cell models to explore the consequences of the identified variants. This included patient-derived cells as well as cells in which they intentionally introduced the detected AXIN1 variants through genome editing. Their analyses showed that these genetic changes resulted in a smaller amount of functional AXIN1 protein and an enhanced activation of the Wnt signaling pathway.

AXIN1 is a crucial component in the regulation of the beta-catenin-dependent Wnt signaling pathway. This signaling cascade controls fundamental cellular processes during embryonic development and also plays an important role in the balance of bone formation and resorption. AXIN1 has been the subject of extensive research, but no germline variants of this gene have been reported in humans to date. The results of the recent study, published in the American Journal of Human Genetics, suggest that AXIN1 influences the activity of osteoblasts and osteoclasts. These two cell types work together in an intricately coupled manner: osteoblasts form bone tissue while osteoclasts destroy it.

Rare skeletal disorders, their genetic causes and underlying molecular mechanisms and the development of specific gene therapy approaches are a key focus of the Kornak research group at the Institute of Human Genetics Göttingen. New insights gained from their research are directly translated into clinical care at the University Medical Center Göttingen: “In our specialized Center for Rare Skeletal Diseases patients and their families receive individual counselling as well as fast clinical, laboratory, and molecular genetic diagnostics and they have access to specific treatment options. With our research, we aim at advancing the development of new therapeutic approaches and their direct integration into clinical practice”, says Professor Kornak.

AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia
Terhal P, Venhuizen AJ, Lessel D, Tan WH, Alswaid A, Grün R, Alzaidan HI, von Kroge S, Ragab N, Hempel M, Kubisch C, Novais E, Cristobal A, Tripolszki K, Bauer P, Fischer-Zirnsak B, Nievelstein RAJ, van Dijk A, Nikkels P, Oheim R, Hahn H, Bertoli-Avella A, Maurice MM, Kornak U.
Am J Hum Genet 2023 Aug 9:S0002-9297(23)00251-3. doi: 10.1016/j.ajhg.2023.07.011. Epub ahead of print.