Mutation on Leu131 has not been reported,

but missense mutations on encompassing residues, I130L, I130F and A132D have been shown to be causative [19], indicating that this region is functionally important. W164R was found in a boy with NDI, and his mother was a heterozygous carrier of the mutation. On Trp164, another mutation, W164S, has been reported [17], and mutations on Ala165 and Ser167 were also shown to be causative SN-38 purchase [19]. Q225R was found in a boy with complete NDI, and his mother was a heterozygous carrier without symptoms, while his healthy brother was not affected. L316R was found in a boy with complete NDI, and his mother was a heterozygous carrier. Leu316 has not been the target of missense mutations, while encompassing residues Ser315 and Asn317 located in the 7th transmembrane domain of AVPR2 protein are the target of disease-causing mutations, S315R and N317K [19]. S329G was

found in a boy with complete NDI. His mother and grandmother were asymptomatic heterozygous carriers of the mutation, and his uncle had the same mutation with complete NDI symptoms. S329P was found in a boy with complete NDI, and his mother was an asymptomatic heterozygous carrier. Another mutation on Ser329, S329R, has been reported [21]. Table 3 New putative disease-causing AVPR2 mutation   Nucleotide change Amino acid change Missense c.255C>A D85E   c.269T>C L90P c.348G>C K116N c.368T>G M123R c.392T>C L131P c.490T>C W164R c.674A>G Q225R c.947T>G L316R c.985A>G S329G c.985_986AG>CC S329P Nonsense c.624G>A W208X Deletion c.91_92 del AC FS/190X Y-27632 concentration c.521delA FS/211X c.1055_1068delGTCCCCAAGATGAG FS/376X 5′UTR-AVPR2_DEL 4,586 Large del of AVPR2 5′UTR-AVPR2_DEL 32,787 Large del of AVPR2 Insertion c.369_370insT FS/191X c.498_499insTC FS/212X c.738_739insG FS/257X A nonsense mutation, W208X, was observed in a boy with complete NDI, and his asymptomatic mother and Cl-amidine cell line sister were heterozygous carriers

of the mutation. To date, all reported nonsense mutations have been shown causative [19]. Five novel deletion PtdIns(3,4)P2 mutations were found, and all these mutations cause either large losses of the gene, including the 5′ untranslated region (two families), or frame shifts that result in premature truncation (two families) or elongation (one family) of the coded proteins (Table 3). In a family with a 32,787 nucleotides deletion (the exact deletion size was determined in Daniel Bichet’s lab in Montreal), two affected brothers showed complete NDI. Their mother and sister were asymptomatic heterozygous carriers of the mutation. In another family having a large deletion (4,586 nucleotides), a boy was affected with complete NDI and his mother was a heterozygous carrier. A 1-nucleotide deletion was observed in a complete NDI boy, and his mother was a heterozygous carrier of the mutation.