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Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin–neurophysin II gene

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Abstract

The objective of this study is to identify the genetic defects in a Chinese family with autosomal dominant familial neurohypophyseal diabetes insipidus. Complete physical examination, fluid deprivation, and DDAVP tests were performed in three affected and three healthy members of the family. Genomic DNA was extracted from leukocytes of venous blood of these individuals for polymerase chain reaction amplification and direct sequencing of all three coding exons of arginine vasopressin–neurophysin II (AVP–NPII) gene. Seven members of this family were suspected to have symptomatic vasopressin-deficient diabetes insipidus. The water deprivation test in all the patients confirmed the diagnosis of vasopressin-deficient diabetes insipidus, with the pedigree demonstrating an autosomal dominant inheritance. Direct sequence analysis revealed a novel mutation (c.193T>A) and a synonymous mutation (c.192C>A) in the AVP–NPII gene. The missense mutation resulted in the substitution of cysteine by serine at a highly conserved codon 65 of exon 2 of the AVP–NPII gene in all affected individuals, but not in unaffected members. We concluded that a novel missense mutation in the AVP–NPII gene caused neurohypophyseal diabetes insipidus in this family, due to impaired neurophysin function as a carrier protein for AVP. The Cys65 is essential for NPII in the formation of a salt bridge with AVP. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the normal expression of vasopressin.

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Acknowledgments

The authors wish to thank Professor Yanhua Qi, MD, of the second affiliated hospital of Harbin medical university for advice and assistance with the laboratory and clinical studies. The study was supported by the science and technology program of Heilong Jiang Province NO.LC08C16 and the financial aid from the overseas program of the Ministry of Education, Heilong Jiang Province NO.1152hq26.

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Authors and Affiliations

  1. Department of Genetics, National Research Institute for Family Planning, Beijing, China

    Binbin Wang & Xu Ma

  2. Department of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

    Yongfeng Luo, Yu Qiu, Chuan Zhang, Chengluo Jin, Yakun Zhao & Qingguo Zhu

Authors
  1. Yongfeng Luo
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  2. Binbin Wang
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  3. Yu Qiu
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  4. Chuan Zhang
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  5. Chengluo Jin
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  6. Yakun Zhao
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  7. Qingguo Zhu
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  8. Xu Ma
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Corresponding author

Correspondence to Qingguo Zhu.

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Yongfeng Luo, Binbin Wang and Yu Qiu contributed equally to this study.

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Luo, Y., Wang, B., Qiu, Y. et al. Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin–neurophysin II gene. Endocrine 42, 208–213 (2012). https://doi.org/10.1007/s12020-012-9606-2

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