PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■我们根据先前发表的数据，描述了由VPS16和MEFV遗传变异引起的肌张力障碍及其家族的临床图片，并讨论了可能带来临床发现的机制。
■一名17岁男性患有广泛性肌张力障碍，始于6岁，非发热性腹痛发作，14岁时被诊断为1型糖尿病。同时,他13岁的妹妹也有同样的临床表现.他父亲患有糖尿病，母亲无症状。父母之间没有血缘关系。用全外显子组测序检测遗传变异。
■VPS16c.1513C>T/p。Arg505*（可能致病），在他的兄弟姐妹中检测到MEFVc.208A>Gp.Met694val（致病性）和MEFVc.172T>Cp.Ile591Thr（意义未知）杂合变体。父亲的VPS16c.1513C>T/p。Arg505*和MEFVc.2080A>GpMet694val变异，母亲有MEFVc.1772T>Cp.Ile591Thr变异。
■这些疾病在兄弟姐妹中的发生，但在父母中却不存在，这表明VPS16和MEFV基因中两个独立变异的共存决定了表型。此外,该家族中MEFV变异负荷的增加以及DM发生在较早年龄的事实表明,炎症可能导致早期糖尿病临床表现.
■一名17岁男性患有广泛性肌张力障碍，始于6岁，非发热性腹痛发作，14岁时被诊断为1型糖尿病。同时,他13岁的妹妹也有同样的临床表现.他父亲患有糖尿病，母亲无症状。父母之间没有血缘关系。用全外显子组测序检测遗传变异。
■VPS16c.1513C>T/p。Arg505*（可能致病），在他的兄弟姐妹中检测到MEFVc.208A>Gp.Met694val（致病性）和MEFVc.172T>Cp.Ile591Thr（意义未知）杂合变体。父亲的VPS16c.1513C>T/p。Arg505*和MEFVc.2080A>GpMet694val变异，母亲有MEFVc.1772T>Cp.Ile591Thr变异。
■这些疾病在兄弟姐妹中的发生，但在父母中却不存在，这表明VPS16和MEFV基因中两个独立变异的共存决定了表型。此外,该家族中MEFV变异负荷的增加以及DM发生在较早年龄的事实表明,炎症可能导致早期糖尿病临床表现.
