Familial Mediterranean fever gene variations could trigger VPS16-associated early-onset dystonia and diabetes mellitus: clinical identification of a family with MEFV and VPS16 genetic variation association

Abstract

Objectives We described the clinical pictures of an index case with dystonia and his family resulting from VPS16 and MEFV genetic variations based on previously published data and discussed the mechanisms that may have brought out the clinical findings. Methods In a 17-year-old male who had generalized dystonia started at age six had nonfebrile abdominal pain attacks and was diagnosed with type 1 diabetes at age 14. Meanwhile, his 13 year-old sister had the same clinical presentation. His father was diabetic and his mother was asymptomatic. There was no consanguinity between the parents. Genetic variations detected with whole exome sequencing. Results VPS16 c.1513C>T/p. Arg505*(likely pathogenic), MEFV c.2080A>G p. Met694val (pathogenic), MEFV c.1772T>C p. Ile591Thr (unknown significance) heterozygous variants were detected in siblings. Father had VPS16 c.1513C>T/p Arg505*, MEFV c.2080A>G p Met694val variations and mother had MEFV c.1772T>C p. Ile591Thr variations. Conclusion The occurrence of these diseases in siblings but in the absence of parents suggests the idea that the coexistence of two separate variations in the VPS16 and MEFV genes determines the phenotype. In addition, the increase in MEFV variation load in this family and the fact that DM occurs at an earlier age suggest that inflammation may cause early diabetic clinical presentation.