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Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2.
Clin Exp Nephrol. 2013 Jun; 17(3):338-44.CE

Abstract

BACKGROUND

Familial form of nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by arginine vasopressin type 2 receptor (AVPR2) or water channel aquaporin 2 (AQP2) gene mutations. It is speculated that 90% of NDI families carry disease-causing mutations in AVPR2 and 10% carry the mutations in AQP2; however, these percentages have not been supported by actual data. It is also unknown whether these percentages vary in different ethnic groups.

METHODS

Gene mutation analyses were performed for 78 Japanese NDI families. All exons and intron-exon boundaries of the AVPR2 and AQP2 genes were directly sequenced.

RESULTS

A total of 62 families (79%) carried disease-causing mutations in AVPR2, while nine families (12%) carried mutations in AQP2. We identified 22 novel putatively disease-causing mutations (19 in AVPR2 and 3 in AQP2). Regarding AVPR2, 52 disease-causing mutations were identified. Among them, missense mutations were most common (54%), followed by deletion mutations. In the 64 women who had monoallelic disease-causing AVPR2 mutations, 16 (25%) had NDI symptoms, including 4 complete NDI subjects. Regarding AQP2, 9 disease-causing mutations were identified in nine families. Two missense mutations and one deletion mutation showed a recessive inheritance, while one missense mutation and five small deletion mutations in the C-terminus of AQP2 showed a dominant inheritance.

CONCLUSIONS

Most Japanese NDI families carry disease-causing mutations in AVPR2 and 12% carry mutations in AQP2. A total of 22 novel putatively disease-causing mutations were identified. The relatively high occurrence of symptomatic carriers of AVPR2 mutations needs attention.

Authors+Show Affiliations

Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. ssasaki.kid@tmd.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23150186

Citation

Sasaki, Sei, et al. "Hereditary Nephrogenic Diabetes Insipidus in Japanese Patients: Analysis of 78 Families and Report of 22 New Mutations in AVPR2 and AQP2." Clinical and Experimental Nephrology, vol. 17, no. 3, 2013, pp. 338-44.
Sasaki S, Chiga M, Kikuchi E, et al. Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. Clin Exp Nephrol. 2013;17(3):338-44.
Sasaki, S., Chiga, M., Kikuchi, E., Rai, T., & Uchida, S. (2013). Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. Clinical and Experimental Nephrology, 17(3), 338-44. https://doi.org/10.1007/s10157-012-0726-z
Sasaki S, et al. Hereditary Nephrogenic Diabetes Insipidus in Japanese Patients: Analysis of 78 Families and Report of 22 New Mutations in AVPR2 and AQP2. Clin Exp Nephrol. 2013;17(3):338-44. PubMed PMID: 23150186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. AU - Sasaki,Sei, AU - Chiga,Motoko, AU - Kikuchi,Eriko, AU - Rai,Tatemitsu, AU - Uchida,Shinichi, Y1 - 2012/11/14/ PY - 2012/10/15/received PY - 2012/10/28/accepted PY - 2012/11/15/entrez PY - 2012/11/15/pubmed PY - 2014/1/23/medline SP - 338 EP - 44 JF - Clinical and experimental nephrology JO - Clin Exp Nephrol VL - 17 IS - 3 N2 - BACKGROUND: Familial form of nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by arginine vasopressin type 2 receptor (AVPR2) or water channel aquaporin 2 (AQP2) gene mutations. It is speculated that 90% of NDI families carry disease-causing mutations in AVPR2 and 10% carry the mutations in AQP2; however, these percentages have not been supported by actual data. It is also unknown whether these percentages vary in different ethnic groups. METHODS: Gene mutation analyses were performed for 78 Japanese NDI families. All exons and intron-exon boundaries of the AVPR2 and AQP2 genes were directly sequenced. RESULTS: A total of 62 families (79%) carried disease-causing mutations in AVPR2, while nine families (12%) carried mutations in AQP2. We identified 22 novel putatively disease-causing mutations (19 in AVPR2 and 3 in AQP2). Regarding AVPR2, 52 disease-causing mutations were identified. Among them, missense mutations were most common (54%), followed by deletion mutations. In the 64 women who had monoallelic disease-causing AVPR2 mutations, 16 (25%) had NDI symptoms, including 4 complete NDI subjects. Regarding AQP2, 9 disease-causing mutations were identified in nine families. Two missense mutations and one deletion mutation showed a recessive inheritance, while one missense mutation and five small deletion mutations in the C-terminus of AQP2 showed a dominant inheritance. CONCLUSIONS: Most Japanese NDI families carry disease-causing mutations in AVPR2 and 12% carry mutations in AQP2. A total of 22 novel putatively disease-causing mutations were identified. The relatively high occurrence of symptomatic carriers of AVPR2 mutations needs attention. SN - 1437-7799 UR - https://www.unboundmedicine.com/medline/citation/23150186/Hereditary_nephrogenic_diabetes_insipidus_in_Japanese_patients:_analysis_of_78_families_and_report_of_22_new_mutations_in_AVPR2_and_AQP2_ L2 - https://dx.doi.org/10.1007/s10157-012-0726-z DB - PRIME DP - Unbound Medicine ER -