{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T21:02:22Z","timestamp":1757451742491,"version":"3.28.0"},"reference-count":0,"publisher":"Ayub Medical College, Abbottabad Pakistan","issue":"2","license":[{"start":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T00:00:00Z","timestamp":1719705600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Ayub Med Coll Abbottabad"],"abstract":"<jats:p>Wolfram syndrome is a progressive neurodegenerative disorder caused by an alteration in the WFS-1 gene, located on chromosome 4p16.1 and is characterized by the acronym DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). WFS-1 gene encodes for a transmembrane protein termed Wolframin found in the membrane of the endoplasmic reticulum. Although Wolfram Syndrome is generally considered an autosomal recessive disorder, a milder non-classic autosomal dominant form has been reported in association with a single pathogenic or likely pathogenic variant in WFS-1 gene. Objective was to date more than 200 variants have been identified in the WFS-1 gene. This case report aims to highlight and explain a novel de-novo likely pathogenic variant of the WFS-1 gene in a Pakistani child, which is highly plausible to induce non-classic WFS-1 spectrum disorder (MedGen UID: 481988). Case Discussion: Our patient, a seven-year-old boy, initially sought medical attention at our endocrine clinic for diabetic control. Besides diabetes, other notable features included short stature, sensorineural deafness and a history of bilateral cataracts. Family history was significant for parental consanguinity. A clinical diagnosis of Wolfram Syndrome was suspected and a multi gene panel test which included the WFS-1 gene was ordered. Initial report noted a variant of uncertain significance in the WFS-1 gene at c.2586G&gt;T (p.Lys862Asn), which was later reclassified as a likely pathogenic variant by the laboratory based on the patient\u2019s clinical presentation. Conclusion: Access to genetic testing is not readily available in Pakistan and our population is under studied and these complex diagnoses are often missed. In this study, we present a novel de novo likely pathogenic variant in the WFS-1 gene that causes non-classic WFS-1 spectrum disorder in a child from our population.<\/jats:p>","DOI":"10.55519\/jamc-02-12379","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T03:56:29Z","timestamp":1731988589000},"page":"433-435","source":"Crossref","is-referenced-by-count":1,"title":["A NOVEL DE NOVO LIKELY PATHOGENIC VARIANT OF WFS-1 GENE IN A PAKISTANI CHILD WITH NON-CLASSIC WFS-1 SPECTRUM DISORDER"],"prefix":"10.55519","volume":"36","author":[{"given":"Misbah Iqbal","family":"Hanif","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamza","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsina Noor","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Jamal","family":"Raza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Ajaz","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"34325","published-online":{"date-parts":[[2024,6,30]]},"container-title":["Journal of Ayub Medical College Abbottabad"],"original-title":[],"link":[{"URL":"https:\/\/jamc.ayubmed.edu.pk\/jamc\/index.php\/jamc\/article\/download\/12379\/3757","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jamc.ayubmed.edu.pk\/jamc\/index.php\/jamc\/article\/download\/12379\/3757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T03:56:29Z","timestamp":1731988589000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamc.ayubmed.edu.pk\/jamc\/index.php\/jamc\/article\/view\/12379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,30]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,6,30]]}},"URL":"https:\/\/doi.org\/10.55519\/jamc-02-12379","relation":{},"ISSN":["1819-2718","1025-9589"],"issn-type":[{"value":"1819-2718","type":"electronic"},{"value":"1025-9589","type":"print"}],"subject":[],"published":{"date-parts":[[2024,6,30]]}}}