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Autosomal Dominant Neurohypophyseal Diabetes Insipidus with Linkage to Chromosome 20p13 but without Mutations in the AVP-NPII Gene

Shanghai Clinical Center for Endocrine and Metabolic Diseases (L.Y., X.L., Y.C., W.W., T.S., L.J., B.C., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, People’s Republic of China; Department of Internal Medicine (H.S.), Inner Mongolia University for Nationalities Affiliated Hospital, Inner Mongolia 028000, Mongolia; and Division of Endocrine and Metabolic Diseases (X.L., G.N.), E-Institute of Shanghai Universities, Shanghai 200025, People’s Republic of China

Address all correspondence and requests for reprints to: Guang Ning, M.D., Ph.D., Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University, Ruijin Er Lu, Shanghai 200025, People’s Republic of China. E-mail: guangning{at}medmail.com.cn.

Context: Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) has been known as a rare disorder transmitted as an autosomal dominant trait, characterized by polyuria and polydipsia, and caused by deficient neurosecretion of arginine vasopressin precursor (AVP-NPII). We reported an ADNDI family with linkage to chromosome 20p13 but without mutations in the AVP-NPII gene.

Objective: The objective of this study was to identify the corresponding locus responsible for ADNDI in a family without AVP-NP II gene mutations.

Subjects and Methods: Two families with ADNDI were diagnosed by water deprivation test. The AVP-NPII gene was amplified by PCR and sequenced. A genomewide scan was performed in one family using 400 microsatellite markers covering 22 autosomes.

Results: A 3-bp deletion (1827–1829delAGG) of AVP-NPII gene was identified in the affected individuals in one family. Although no mutations could be detected in the coding, the promoter, and intronic regions of AVP-NPII gene in the other family, a maximum LOD score of 1.202999 ( = 0.00) was obtained at marker D20S889 by genomewide scan, and a 7-cM interval on chromosome 20p13 was defined by fine mapping with markers D20S199–D20S849. Furthermore, the intragenic region that regulates AVP-NPII and oxytocin expression as an enhancer element and the UBCE7IP5 gene that participates in prohormone degradation were sequenced. No alterations could be detected either.

Conclusion: The corresponding locus responsible for ADNDI is possibly heterogeneous regarding the slightly different clinical features in these two families.