PURPOSE Familial neurohypophysial diabetes insipidus (FNDI), commonly caused by autosomal dominant arginine vasopressin (AVP) mutations, is a rare condition in which vasopressin fails in regulating body's level of water with final polyuria and polydipsia. Genetic testing in familial cases of FNDI should be carry out to ensure adequate treatments and avoid disease manifestations especially in infants. METHODS In this study, we investigated three-generations of a large Italian family with clinical diagnosis of familial central diabetes insipidus for the presence of potential pathogenic mutations in the AVP gene. RESULTS We identified a heterozygous missense mutation (c.154 T > A; p.C52S) in AVP gene in all affected members studied of a large Italian family. In silico tools were used to investigate the pathogenic role of the mutation and three-dimensional protein structure predicted that the p.C52S impairs disulfide bridges formation resulting in misfolding of the protein. CONCLUSIONS This is the first study that identified a novel missense p.C52S mutation as causative of central diabetes insipidus in a large Italian pedigree.

中文翻译：

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常染色体显性遗传家族性神经垂体性尿崩症是由一个意大利大家族中的 AVP 基因的新错义突变引起的。

目的家族性神经垂体尿崩症 (FNDI)，通常由常染色体显性精氨酸加压素 (AVP) 突变引起，是一种罕见的情况，其中加压素不能调节身体的水水平，最终导致多尿和烦渴。应该对家族性 FNDI 病例进行基因检测，以确保得到充分的治疗并避免疾病表现，尤其是在婴儿中。方法 在这项研究中，我们调查了一个临床诊断为家族性中枢性尿崩症的意大利大家庭的三代人是否存在潜在的 AVP 基因致病突变。结果 我们在一个意大利大家庭的所有受影响成员中发现了 AVP 基因中的杂合错义突变 (c.154 T > A; p.C52S)。计算机工具用于研究突变的致病作用，并且三维蛋白质结构预测 p.C52S 会损害二硫键的形成，从而导致蛋白质的错误折叠。结论 这是第一项在一个大型意大利谱系中发现一种新的错义 p.C52S 突变是中枢性尿崩症的病因的研究。