Abstract
Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron–exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.
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Acknowledgements
We thank the patient and his family for agreeing to participate in this study. We thank the Chronic Care Centre, Beirut, Lebanon, for their collaboration and support. This study was supported by institutional funds from Inserm and University Paris 7, a joint grant from the Juvenile Diabetes Research Foundation, the Fondation pour la Recherche Médicale and Inserm and a grant from the Agence Nationale de la Recherche to CJ. We thank the AP-HP for their support.
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Sanyoura, M., Woudstra, C., Halaby, G. et al. A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient. Eur J Hum Genet 22, 140–143 (2014). https://doi.org/10.1038/ejhg.2013.87
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DOI: https://doi.org/10.1038/ejhg.2013.87
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