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New genetic tumor syndrome identified

In an international study led by Prof. Dr. Hanno Bolz, mutations in the MAD2L1BP  gene have been identified as the cause of a new tumor syndrome. The genetic defect leads to chromosomal maldistribution in a large proportion of cells in those affected; the resulting disease is therefore classified as mosaic variegated aneuploidy (MVA).

The MAD2L1BP protein is part of a dynamic protein complex that controls correct chromosome segregation. Its impairment leads to MVA in an Egyptian patient and her affected brother. Aneuploidies are considered a risk factor for cancer development, and the siblings actually developed extremely rare gonadal tumors in early childhood, a juvenile granulosa cell tumor (JGCT) of the ovary or testis.

A Saudi patient with a pronounced brain malformation, severe developmental disorder and epilepsy (which were also present in the Egyptian patient) died very early and possibly before a tumor could develop. This patient, but not the Egyptian siblings, also exhibited repeated blood sugar abnormalities, which have also been described in mice with an inactivated MAD2L1BP  gene.

Together with partners from the University of Bayreuth and the University Medical Center Mainz, the cellular effects of the genetic defect were characterized in functional detail. The study provides important new insights into hereditary tumor diseases, a diagnostic, advisory and scientific focus of Bioscientia Human Genetics.

The publication can be read in the specialist journal JCI Insight.

If you have any questions about the publication, please contact Prof. Dr. Hanno Bolz by e-mail: hanno.bolz@bioscientia.de. If you have any questions about human genetic counseling and diagnostics, please contact the Bioscientia Human Genetics team.

Text by: Laura Ranzenberger

Tuesday, October 17, 2023

New cause of retinal dystrophy identified

In an international study led by Prof. Dr. Hanno Bolz, Medical Director of Bioscientia Human Genetics since the beginning of 2023, mutations in the CEP162 gene have been identified as a new cause of retinitis pigmentosa (RP). RP is the most common form of hereditary retinal degeneration.

Together with partners, particularly from the USA and Belgium, it was possible to show in detail how the CEP162 defect leads to a gradual loss of function of the retinal cells. The consequences are night blindness, progressive narrowing of the visual field and ultimately almost complete loss of vision.

The study was the result of routine diagnostics in which no cause was found in the known RP genes. The intensive search for the genetic basis led to the identification of a previously unknown cause of RP. This procedure is exemplary for Bioscientia's human genetics department, as hereditary eye diseases (especially retinal diseases) are a diagnostic, counseling and scientific focus.

Benefits for patients

The identification of the gene closes another gap. Thanks to the publication, CEP162 is now being used in diagnostics worldwide. This means that patients with RP caused by a defect in the CEP162 gene now also receive a clear genetic diagnosis.

With a clear diagnosis, the prognosis can be assessed better and the risk of recurrence can be determined (in this case: very low risk of recurrence of the disease in the patients' own children). In addition, those affected can register in patient registers (e.g. that of PRO RETINA) in order to benefit from future therapeutic approaches as early as possible. Furthermore, the identification of a causative gene is the first prerequisite for the development of a gene-specific therapeutic approach. The publication can be read in the Journal of Clinical Investigation.

If you have any questions about the publication, please contact Prof. Dr. Hanno Bolz by e-mail: hanno.bolz@bioscientia.de.

If you have any questions about human genetic counseling and diagnostics, please contact the Bioscientia Human Genetics team.

Text by: Laura Ranzenberger

Monday, June 12, 2023