Background: The two most commonly known types of Diabetes Mellitus (DM) are DM type 1 and DM type 2, characterized by insulin deficiency and insulin insensitivity, respectively. DM can also be associated with rare mutlisystemic syndromes such as Alstrom, Bardet-Biedl, Wolfram and pigmentary hypertrichosis insulin dependent diabetes (PHID) syndromes.
Objectives: To understand the genetic and molecular basis of syndromic DM in a large cohort of patients.
Methods: Homozygosity mapping, followed by confirmation using Sanger sequencing were used to find novel and rare mutations. Protein expression was then studied using Western Blots.
Results: So far, five patients from Turkey have been identified to have novel causes of Wolfram Type 1, which is a progressive disorder characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA) and deafness (D) and is known as DIDMOAD. Western Blots show no protein expression. Moreover, 1 patient from Turkey has been identified to have Wolfram Type 2, which differs from Wolfram Type 1 by the absence of DI. Also, 2 siblings from Turkey have been found to have novel variances in the untranslated regions of the gene responsible for the pigmented hypertrichosis insulin dependent diabetes (PHID) syndrome uncovering a novel molecular mechanism for this condition.
Conclusion: This study so far identified novel causes of Wolfram Type 1 and PHID syndrome. Further work is ongoing to understand the molecular and genetic mechanisms of these and other rare DM syndromes.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology