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. 2024 Jul 13;8(3):rkae083.
doi: 10.1093/rap/rkae083. eCollection 2024.

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

Yagmur Inalkac Gemici  1 , Cemal Ekici  2 , Melike Batum  1 , Cenk Akbostanci  3 , Ahmet Koc  2 , Hatice Mavioglu  1
Affiliations

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

Yagmur Inalkac Gemici et al. Rheumatol Adv Pract. .

Abstract

Objectives: We describe 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 discuss the mechanisms that may have brought out the clinical findings.

Methods: A 17-year-old male had generalized dystonia that started at age 6 years, non-febrile abdominal pain attacks and was diagnosed with type 1 diabetes at age 14 years. 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 were detected with whole exome sequencing.

Results: VPS16 c.1513C>T/p.Arg505* (likely pathogenic), MEFV c.2080A>G p.Met694val (pathogenic) and MEFV c.1772T>C p.Ile591Thr (unknown significance) heterozygous variants were detected in his siblings. The father had VPS16 c.1513C>T/p.Arg505* and MEFV c.2080A>G p Met694val variations and the mother had MEFV c.1772T>C p.Ile591Thr variations.

Conclusions: The occurrence of these diseases in siblings but their absence in the 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 an early diabetic clinical presentation.

Keywords: FMF; MEFV; VPS16; diabetes mellitus; dystonia.

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Figures

Figure 1.
Figure 1.
The genetic and phenotypic characteristics of cases
Figure 2.
Figure 2.
Pedigree of the index case and his family
See this image and copyright information in PMC

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