In the present study, the functions of the mutant proteins were not examined, which is a limitation of the present study. Disease-causing AVPR2 mutations in 62 NDI Selisistat ic50 families A total of 52 putative disease-causing AVPR2 mutations were identified in 62 families (several mutations were shared by different

independent families). Table 2 summarizes the types of AVPR2 mutations. Gene variants/polymorphisms that have been reported not to cause NDI [19] were excluded in this summary. Missense mutations were most common, accounting for half of the mutations, followed by deletion mutations, insertion mutations, and nonsense DMXAA mutations. Splicing mutations were the least common. This relative frequency of disease-causing AVPR2 mutations is consistent with the results of a worldwide summary of AVPR2 mutations, as shown

in Table 2 [19], again confirming that the genetic mechanisms causing buy SRT1720 NDI are the same in different ethnic groups [19]. Table 2 Types of AVPR2 mutations in Japanese Nephrogenic diabetes insipidus (NDI) patients and comparison with a global summary Types of mutations Number of mutations identified in Japanese patientsa Relative frequency in a global summaryb (%) Missense 28 (54 %) 56  Nonsense 4 (8 %) 13  Deletion 13 (25 %) 29  Insertion 5 (10 %) 4 Splicing 2 (4 %) 1 aA total 52 mutations were identified in this study bRelative frequency reported by Spanakis et al. [19] Of these AVPR2 mutations, 19 mutations were novel, and the other mutations were previously reported or recurrences of the previously reported mutations. Details of the novel AVPR2 mutations are summarized in Table 3. In brief, in a family carrying the missense mutation D85E, an index subject was a female patient manifesting complete NDI, and her father also manifested NDI. The index subject was heterozygous for this mutation. The codon Asp85 seems

functionally important, because another Thalidomide missense mutation on this residue, D85N, was reportedly causative in six families [19]. L90P was observed in two unrelated families. In one family, the index case was a mother of a boy with NDI; they manifested partial and complete NDI, respectively, and the mother was a heterozygous carrier of the mutation. In another family, a boy showed complete NDI, and his mother was a heterozygous carrier of the mutation with no NDI symptoms. K116N mutation was found in a boy with complete NDI, and his mother was not a carrier of the mutation, implying that the mutation occurred de novo. M123R mutation was observed in two unrelated families in which the index patients were boys with complete NDI. DNA samples of other members of the families were not available, and a mother in one family had polyuria and polydipsia. M123R has not been previously reported, but another mutation on this residue, M123K, has been reported [11].