Uncovering a Milder Wolfram Syndrome Variant in Jewish Populations (Part 4)

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For context, Parts 1 , 2, and 3 of this series can be found here:

Part 1: https://wolframsyndrome.wustl.edu/uncovering-a-milder-wolfram-syndrome-variant-in-jewish-populations-part-1/

Part 2: https://wolframsyndrome.wustl.edu/uncovering-a-milder-wolfram-syndrome-variant-in-jewish-populations-part-2/

Part 3: https://wolframsyndrome.wustl.edu/uncovering-a-milder-wolfram-syndrome-variant-in-jewish-populations-part-3/

We have identified a mild form of Wolfram syndrome in Jewish populations, linked to the pathogenic WFS1 variant, WFS1 c.1672C>T (Arg558Cys). My impression is that many Jewish patients with atypical diabetes and/or optic nerve atrophy of unknown cause may unknowingly carry this mild variant of Wolfram syndrome. Recognizing these patients is critical for several reasons:

1. Management Plan
Tailored management of diabetes or prediabetes is essential for individuals with the Jewish variant of Wolfram syndrome. Early detection of optic nerve atrophy is equally important to establish a comprehensive care plan with a neuro-ophthalmologist.

2. Family Planning
Identifying affected individuals provides an opportunity to screen family members for the Jewish variant of Wolfram syndrome. This process, guided by genetic counselors and geneticists, can inform family planning and risk assessment.

3. Development of Novel Therapies
We are actively developing novel therapies, including oral medications and gene-editing approaches, specifically targeting the Jewish variant of Wolfram syndrome. Identifying more patients can facilitate the collection of critical data and biological samples, advancing these therapeutic efforts.

4. Designing Clinical Trials
A larger cohort of identified patients will enable the design of a clinical trial specifically targeting the Jewish variant of Wolfram syndrome, paving the way for innovative treatment strategies.

5. Establishment of Screening Programs
A robust screening program for the Jewish variant of Wolfram syndrome can lead to earlier diagnosis and intervention, improving outcomes for affected individuals.

Each of these steps plays a vital role in improving care, advancing research, and offering hope to those impacted by this variant of Wolfram syndrome. I look forward to discussing these topics in greater detail in my upcoming blogs.

Fumihiko (Fumi) Urano, MD, PhD
Samuel E. Schechter Professor of Medicine
Director, Wolfram Syndrome and Related Disorders Clinic and Research
Washington University Medical Center