This table summarizes the mutations that have been reported in the literature or found in our lab
No. Exon Codona Nucleotideb change Amino acid or other change Restriction site alterationc (%) Enzyme activity /[%] 15N ammonia incorporationd Comment Disease presentatione Referencef
1     delOTC gene         Neonatal Yamaguchi et al. [2006]
2     delExon 1-3         Neonatal Tuchman et al. [1997]
3 Exon 1 1 c.1A>G p.Met1Val MboII, SfaNI     Female Oppliger Leibundgut et al. [1997]
4   1 c.1A>T p.Met1Leu MboII, SfaNI     Neonatal Yamaguchi et al. [2006]
5   1 c.2T>C p.Met1Thr SfaNI     Female Yamaguchi et al. [2006]
6   1 c.3G>A p.Met1Ile Bst4CI, HpyCH4III, SfaNI     Female Climent and Rubio [2002b]
7   10,11 c.28_31delAACA Frameshift       Female Yamaguchi et al. [2006]
8   10 c.29dupA Frameshift       Female Yamaguchi et al. [2006]
9   14 c.40delT Frameshift     Leader sequence Neonatal Hwu et al. [2003]
10   18 c.53delA Frameshift AvaII     Neonatal Tuchman et al. [2002]
11   23 c.67C>T p.Arg23X AsuII, TaqI   Leader sequence, CpG dinucleotide Neonatal Grompe et al. [1991]
12   26 c.77G>A p.Arg26Gln   (0%) Leader sequence, CpG dinucleotide, possible donor splice site error Neonatal Grompe et al. [1989]
13   26 c.77G>C p.Arg26Pro     Leader sequence, CpG dinucleotide, possible donor splice site error Neonatal Yamaguchi et al. [2006]
14 Intron 1   c.77+1G>T   MseI    Donor splice site error Female Tuchman et al. [1997]
15     c.77+1G>A       Donor splice site error Female Yamaguchi et al. [2006]
16     c.77+2dupT   MseI   Donor splice site error Neonatal Yamaguchi et al. [2006]
17     c.77+3_6delAAGT   HpHI   Donor splice site error Female Tuchman et al. [2002]
18     c.77+4A>C   RsaI (0%) Donor splice site error Neonatal Hoshide et al. [1996]
19     c.77+5G>A       Donor splice site error Neonatal Tuchman et al. [1997]
20     c.78-3C>G Frameshift (due to 77_78>insAG) MnlI (<5%) Acceptor splice site error, termination of translation Female Bisanzi et al. [2002]
21     c.78-1G>C       Acceptor splice site error Neonatal Yamaguchi et al. [2006]
22 Exon 2 32 c.94C>T p.Gln32X       Female Oppliger Leibundgut et al. [1997]
23   36 c.106C>T p.Gln36X CviRI, Fnu4HI, HpyCH4V     Female Genet et al. [2000]
24   39 c.115G>T p.Gly39Cys HaeIII, Sau96I     Late Calvas et al. [1998]
25   40 c.118C>T p.Arg40Cys HaeIII   CpG dinucleotide Late Oppliger Leibundgut et al. [1995]
26   40 c.119G>A p.Arg40His Mae III, Tsp45I (6%) CpG dinucleotide, expression studies show normal kinetics and thermal stability, protein degradation in cytosol Late Tuchman et al. [1994b]
27   41 c.122A>G p.Asp41Gly       Female Yamaguchi et al. [2006]
28   43 c.127C>T p.Leu43Phe       Female Oppliger Leibundgut et al. [1997]
29   44 c.131C>T p.Thr44Ile       Female Yoo et al. [1996]
30   45 c.133C>G p.Leu45Val HpyCH4III, TspRI     Female Tuchman et al. [1998]
31   45 c.134T>C p.Leu45Pro       Neonatal Grompe et al. [1989]
32   45 c.135dupA Frameshift       Female Yamaguchi et al. [2006]
33   45-47 c.135delA Frameshift   (0%)   Neonatal Calvas et al. [1998]
34   47 c.140_141insG Frameshift  AluI, HindIII     Neonatal Shimadzu et al. [1998]
35   47 c.140A>T p.Asn47Ile       Neonatal Tuchman et al. [1997]
36   47 c.140A>C p.Asn47Thr       Female Yamaguchi et al. [2006]
37   48 c.143T>C p.Phe48Ser       Female Genet et al. [2000]
38   49 c.145A>C p.Thr49Pro       Female Yamaguchi et al. [2006]
39   50 c.148G>A p.Gly50Arg HpaII, MspI     Late Tuchman et al. [1997]
40   50 c.148G>T p.Gly50X DdeI, HpaII     Female Feldmann et al. [1992]
41   52 c.154G>A p.Glu52Lys MboII     Neonatal McCullough et al. [2000]
42   52 c.154G>T p.Glu52X MboII     Female McCullough et al. [2000]
43   52 c.155A>G p.Glu52Gly       Neonatal Yamaguchi et al. [2006]
44   52 c.156A>T p.Glu52Asp Tsp509I (4%)   Late McCullough et al. [2000]
45   53 c.158T>C p.Ile53Thr MseI, TspEI, Tsp509I      Late Yamaguchi et al. [2006]
46   53 c.158T>G p.Ile53Ser MseI, TspEI, Tsp509I      Neonatal Yamaguchi et al. [2006]
47   55 c.163T>G p.Tyr55Asp   (28%)   Late Nishiyori et al. [1998]
48   56 c.167T>C p.Met56Thr   [54%]   Late Tuchman et al. [1997]
49   57 c.170T>A p.Leu57Gln BsrDI, CviRI, HpyCH4V      Neonatal Yamaguchi et al. [2006]
50   58 c.174G>A p.Trp58X CviJI     Neonatal Yamaguchi et al. [2006]
51   60 c.179C>T p.Ser60Leu       Female Tuchman et al. [1997]
52   63 c.188T>C p.Leu63Pro BglII     Female Oppliger Leibundgut et al. [1997]
53   67 c.200T>G p.Ile67Arg       Female Yamaguchi et al. [2006]
54   69 c.205C>T p.Gln69X       Female Climent et al. [1999]
55 Intron 2   c.216+1G>A       Donor splice site error Late Oppliger Leibundgut et al. [1996a]
56     c.216+1G>T   MnlI (10%) Donor splice site error Late Azevedo et al. [2002]
57     c.217-1G>A   PsiI, SspI   Acceptor splice site error Neonatal Tuchman et al. [1992]
58 Exon 3   delExon 3         Neonatal Tuchman et al. [1998]
59   76 c.227T>C p.Leu76Ser BsrDI     Neonatal Genet et al. [2000]
60   77 c.231G>T p.Leu77Phe CviRI, MwoI [35%]   Late McCullough et al. [2000]
61   78 c.232C>T p.Gln78X Mwol     Neonatal Yamaguchi et al. [2006]
62   79 c.236G>A p.Gly79Glu   (0%)   Neonatal Tuchman et al. [1992]
63   80 c.238A>G p.Lys80Glu HinfI, PleI     Female Schultz and Salo [2000]
64   80 c.240G>T p.Lys80Asn EcoRI, Tsp509I     Late Galloway et al. [2000]
65   81-82 c.243_245delCTT p.Leu244del Bsu36I, DdeI     Female Tuchman and Plante [1995]
66   82 c.245T>G p.Leu82X BseMII, MnlI     Female Tuchman et al. [2002]
67   83 c.247G>C p.Gly83Arg Bsu36I     Neonatal Tuchman et al. [1997]
68   83 c.248G>A p.Gly83Asp CvnI     Neonatal Bartholomew and McClellan [1998]
69   87 c.259G>A p.Glu87Lys MseI     Late Feldmann et al. [1992]
70   88 c.264A>T p.Lys88Asn   (3%)   Late Reish et al. [1993]
71   90 c.268A>G p.Ser90Gly   (<20%)   Female Takanashi et al. [2002]
72   90 c.269G>A p.Ser90Asn RsaI, ScaI     Neonatal McCullough et al. [2000]
73   90 c.270T>G p.Ser90Arg RsaI, ScaI     Female Tuchman et al. [1998]
74   91 c.271delA Frameshift RsaI, ScaI, TatI   Female Genet et al. [2000]
75   92 c.274C>G p.Arg92Gly TaqI   CpG dinucleotide Female Yamaguchi et al. [2006]
76   92 c.274C>T p.Arg92X TaqI (0%) CpG dinucleotide Neonatal Grompe et al. [1991]
77   92 c.275G>T p.Arg92Leu TaqI   CpG dinucleotide Neonatal Yamaguchi et al. [2006]
78   92 c.275G>A p.Arg92Gln TaqI (0%) CpG dinucleotide Neonatal Grompe et al. [1991]
79   92 c.275G>C p.Arg92Pro MmeI, TaqI   CpG dinucleotide Neonatal Yamaguchi et al. [2006]
80   93 c.277A>G p.Thr93Ala AvaI, XhoI   Carbamyl phosphate binding site Late Tuchman and Plante [1995]
81   94 c.281G>C p.Arg94Thr     Carbamyl phosphate binding site Late Tuchman et al. [1992]
82   95 c.284T>C p.Leu95Ser DpnI, MboI     Late McCullough et al. [2000]
83   98 c.292G>A p.Glu98Lys SfeI (33%)   Female Bisanzi et al. [2002]
84 Intron 3   c.298+1G>A       Donor splice site error Neonatal Garcia-Perez et al. [1995]
85     c.298+1G>T       Donor splice site error Late Yamaguchi et al. [2006]
86     c.298+1_5delGTAAG   HpyCH4III   Donor splice site error Female Tuchman et al. [1997]
87     c.298+5G>C   Hpy8I, MaeIII   Donor splice site error Female Yamaguchi et al. [2006]
88 Exon 4   delExon 4-10         Neonatal Tuchman et al. [1997]
89 100 c.299G>A p.Gly100Asp AccI, EspI     Female Oppliger Leibundgut et al. [1997]
90   102 c.305C>A p.Ala102Glu EspI     Neonatal Tuchman et al. [1997]
91   105 c.314G>T p.Gly105Val       Female Yamaguchi et al. [2006]
92   106 c.316G>A p.Gly106Arg MboII, MnlI     Female McCullough et al. [2000]
93   106 c.317G>A p.Gly106Glu   (<20%)   Female Takanashi et al. [2002]
94   106 c.317G>T p.Gly106Val       Female Yamaguchi et al. [2006]
95   109-110 c.327delT Frameshift       Neonatal Calvas et al. [1998]
96   117 c.350A>G p.His117Arg MslI, TspDTI (18%)   Late Matsuura and Matsuda [1998]
97   117 c.350A>T p.His117Leu MslI, TspDTI     Late Tuchman et al. [1994a]
98   120 c.358_359delGT Frameshift HphI   Termination of translation Female Yamaguchi et al. [2006]
99   122 c.364_365insTT Frameshift MseI     Female Yamaguchi et al. [2006]
100   125 c.374C>T p.Thr125Met MboI, NlaII (<1%)   Neonatal Gilbert-Dussardier et al. [1996]
101   125 c.375delG Frameshift       Female Yamaguchi et al. [2006]
102   126 c.377A>G p.Asp126Gly BseSI, SduI     Neonatal Matsuura et al. [1994]
103   129 c.386G>C p.Arg129Pro MspI, NlaIV   CpG dinucleotide, possible donor splice site error Female Yamaguchi et al. [2006]
104   129 c.386G>A p.Arg129His MspI (1.3√¢¬Ä¬ì3.5%) CpG dinucleotide, donor splice site error, identical to mutation in spfASH mouse Late Tuchman et al. [1994b]
105   129 c.386G>T p.Arg129Leu MspI   CpG dinucleotide, donor splice site error Late Strautnieks and Malcolm [1993]
106 Intron 4   c.386+1G>T   BssKI, CauII, HpaII, ScrFI   Donor splice site error, somatic mosaicism Late Yamaguchi et al. [2006]
107     c.386+1G>A   BssKI, CauII, HpaII, ScrFI   Donor splice site error Neonatal Yamaguchi et al. [2006]
108     c.386+2T>C       Donor splice site error Neonatal Yamaguchi et al. [2006]
109     c.387-2A>T   TspRI   Acceptor splice site error, skipping first 12 bp of exon 5 Neonatal Carstens et al. [1991]
110     c.387-2A>C   TspRI   Acceptor splice site error Neonatal McCullough et al. [2000]
111     c.387-2A>G   BtgI, DsaI, TspRI   Acceptor splice site error Neonatal McCullough et al. [2000]
112 Exon 5   delExon 5-8       Somatic mosaicism Late Maddalena et al. [1988a]
113 130 - 131 c.390_391insTTA p.Val130_Leu131ins Leu       Female Tuchman et al. [2002]
114   131 c.392T>C p.Leu131Ser       Late Yamaguchi et al. [2006]
115   132 c.394T>C p.Ser132Pro       Late Bisanzi et al. [2002]
116   132 c.395C>T p.Ser132Phe BfaI [78.6%]   Late Gyato et al. [2004]
117   135 c.403delG Frameshift NspI, SphI     Neonatal Tuchman et al. [1992]
118   135 c.404C>A p.Ala135Glu MboII     Late Yamaguchi et al. [2006]
119   136 c.407A>T p.Asp136Val SfaNI     Late Yamaguchi et al. [2006]
120   137 c.409G>A p.Ala137Thr SfaNI     Female Yamaguchi et al. [2006]
121   139 c.416T>C p.Leu139Ser       Female Tuchman et al. [1997]
122   140 c.418G>C p.Ala140Pro       Neonatal Yamaguchi et al. [2006]
123   141 c.421C>G p.Arg141Gly TaqI, XhoI   CpG dinucleotide Female Yamaguchi et al. [2006]
124   141 c.421C>T p.Arg141X TaqI, XhoI   CpG dinucleotide Neonatal Hata et al. [1989]
125   141 c.422G>A p.Arg141Gln TaqI, XhoI (0%) CpG dinucleotide Neonatal Maddalena et al. [1988b]
126   141 c.422G>C p.Arg141Pro TaqI, XhoI     Female Tuchman et al. [1997]
127   142 c.425T>A p.Val142Glu       Late Tuchman et al. [2002]
128   144 c.430A>T p.Lys144X MseI     Female Tuchman and Plante [1995]
129   146 c.437C>G p.Ser146X Hpy188I     Neonatal Genet et al. [2000]
130   148 c.443T>C p.Leu148Ser       Neonatal Yamaguchi et al. [2006]
131   148 c.443T>G p.Leu148Trp BsmFI     Female McCullough et al. [2000]
132   148 c.444G>C p.Leu148Phe TaqI     Female Komaki et.al. [1997]
133   148 c.444G>T p.Leu148Phe   (17%)   Female Matsuura and Matsuda [1998]
134   150-151 c.449delC Frameshift ApyI, EcoRII     Female Tuchman et al. [2002]
135   151 c.452T>G p.Leu151Arg       Female Yamaguchi et al. [2006]
136   152 c.455C>T p.Ala152Val CviJI, MseI (3.7%)  Expression studies show reduced OTC protein Late  Kogo et al. [1998]
137   154 c.460G>T p.Glu154X   (0%)   Neonatal Grompe et al. [1989]
138   155 c.463G>T p.Ala155Ser  HinfI, TfiI     Female Tuchman et al. [2002]
139   155 c.463G>C p.Ala155Pro MwoI, SfaNI     Female Yamaguchi et al. [2006]
140   155 c.464C>A p.Ala155Glu BseGI, FokI, HinfI, MboII, MwoI, SfaNI, TfiI     Neonatal Yamaguchi et al. [2006]
141   159 c.476T>C p.Ile159Thr Tsp509I (1.5%)   Late Garcia-Perez et al. [1995]
142   160 c.479T>G p.Ile160Ser BsrDI     Female Climent and Rubio [2002b]
143   160 c.479T>A p.Ile160Asn       Neonatal Yamaguchi et al. [2006]
144   160 c.479T>C p.Ile160Thr       Neonatal Yamaguchi et al. [2006]
145   161 c.481A>G p.Asn161Asp TaqI     Neonatal Genet et al. [2000]
146   161 c.482A>G p.Asn161Ser TspRI     Neonatal Tuchman and Plante [1995]
147   161 c.483T>AorG p.Asn161Lys   (<10%)   Female Takanashi et al. [2002]
148   162 c.484G>C p.Gly162Arg       Female Yamaguchi et al. [2006]
149   162 c.484G>A p.Gly162Arg       Neonatal Feldmann et al. [1992]
150   162 c.485G>A p.Gly162Glu AluI   Neonatal Yamaguchi et al. [2006]
151   164 c.490T>C p.Ser164Pro Fnu4HI     Neonatal Yamaguchi et al. [2006]
152   164 c.491C>G p.Ser164X Hpy188I     Female Matsuda and Tanase [1997]
153   165 c.493G>T p.Asp165Tyr Hpy188I     Late Genet et al. [2000]
154   167 c.501C>A p.Tyr167X MaeIII, RsaI (0%)   Neonatal Garcia-Perez et al. [1995]
155   167 c.501C>G p.Tyr167X RsaI, SfaNI     Neonatal Shimadzu et al. [1998]
156   168 c.503A>C p.His168Pro BccI, BseGI, BstF51, FokI     Late Yamaguchi et al. [2006]
157   168 c.503A>G p.His168Arg BccI, BseGI, BstF51, FokI   Expression studies show enzyme cannot form a functional complex. Female Vella et al. [1996]
158   168 c.504T>A p.His168Gln BccI, BseGI, BstF5I, FokI [69%]   Late Tuchman et al. [1997]
159   169 c.505C>G p.Pro169Ala FokI, NlaIII     Female Tuchman et al. [2002]
160   169 c.506C>T p.Pro169Leu BseGI, BstF51, FokI     Neonatal Genet et al. [2000]
161   172 c.514A>T p.Ile172Phe DpnI, XhoII     Female Climent et al. [1999]
162   172 c.516C>G p.Ile172Met BspNI, DpnI, EcoRII     Neonatal Matsuura et al. [1994]
163   174 c.520G>C p.Ala174Pro EcoRII, BspNI     Female Tsai et al. [1993]
164   175 c.524A>G p.Asp175Gly BstEII, MaeIII     Late Genet et al. [2000]
165   175 c.524A>T p.Asp175Val       Female Tuchman et al. [1997]
166   176 c.526T>C p.Tyr176His  BclI, MboI     Neonatal Tuchman et al. [2002]
167   176 c.527A>G p.Tyr176Cys   (19%)   Late Oppliger Leibundgut et al. [1996b]
168   178 c.533C>T p.Thr178Met NlaIII     Neonatal Oppliger Leibundgut et al. [1995]
169   177-178 c.530_533dupTCAC Frameshift BsaXI     Neonatal Gilbert-Dussadier et al. [1996]
170   178-179 c.532_537delACGCTC p.Thr178_Leu179del  BspNI, EcoRII     Neonatal Shimadzu et al. [1998]
171   179 c.536T>C p.Leu179Pro       Neonatal Yamaguchi et al. [2006]
172   180 c.[539A>C (+) 540G>C] p.Gln180Pro BseBI, BssKI, Eco57MI, EcoRII, GsuI, ScrFI (<10%)   Neonatal Hübler et al. [2001]
173   180 c.540G>C p.Gln180His BseBI, BssKI, Eco57MI, EcoRII, GsuI, ScrFI (7.1%) [43%] Donor splice site error Neonatal Tuchman et al. [1997]
174 Intron 5   c.540+1G>C   AluI, BspNI, EcoRII   Donor splice site error Neonatal Oppliger Leibundgut et al. [1996a]
175     c.540+2T>C   CviJI (0%) Donor splice site error Neonatal Matsuura et al. [1995]
176     c.540+2T>A   Fokl   Donor splice site error Neonatal Yamaguchi et al. [2006]
177     c.541-2A>G       Acceptor splice site error Neonatal Genet et al. [2000]
178 Exon 6 181 c.542A>G p.Glu181Gly BsmFI     Neonatal Tuchman et al. [1998]
179   182 c.545A>T p.His182Leu       Neonatal Tuchman et al. [1994a]
180   183 c.547T>G p.Tyr183Asp SfcI     Female Oppliger Leibundgut et al. [1997]
181   183 c.548A>G p.Tyr183Cys HpyCH4III, TspRI, Tsp4CI     Neonatal Reish et al. [1993]
182   188 c.562G>C p.Gly188Arg HpyCH4IV, TaiI (2%)   Neonatal Gilbert-Dussadier et al. [1996]
183   188 c.563G>T p.Gly188Val       Female Climent et al. [1999]
184   191 c.571C>T p.Leu191Phe DdeI, MnlI (5.7%)   Late Climent and Rubio [2002b]
185 191 c.572T>G p.Leu191Arg AciI, BbvI, BbvCI, Bpu10I, BseMII, BspNI, DdeI, FauI, Fnu4HI, MnlI, TseI     Neonatal Yamaguchi et al. [2006]
186   192 c.576C>G p.Ser192Arg Alu I, PvuII     Neonatal Matsuura et al. [1993]
187   193 c.577T>C p.Trp193Arg AluI, HpaII, NspBII, PvuII     Female Yamaguchi et al. [2006]
188   193 c.577T>G p.Trp193Gly AluI, CviJI, FauI, PvuII     Female Yamaguchi et al. [2006]
189   193 c.578G>A p.Trp193X AlwI, PvuII     Neonatal Shimadzu et al. [1998]
190   195 c.583G>A p.Gly195Arg   (0%) CpG dinucleotide, expression studies show no activity and reduced OTC protein Neonatal Tuchman et al. [1994b]
191   195 c.583delG Frameshift Hpy178III     Female Climent and Rubio [2002b]
192   196 c.586G>A p.Asp196Asn BccI, BseGI, BstF51, FokI, Hpy178III     Late Yamaguchi et al. [2006]
193   196 c.586G>T p.Asp196Tyr BccI, BseGI, BstF51, FokI,     Neonatal Tuchman et al. [1998]
194   196 c.587A>T p.Asp196Val BccI, BseGI, BstF5I, FokI (7%) Increased Km for ornithine Neonatal Matsuura et al. [1993]
195   197 c.589G>A p.Gly197Arg BseG, BstF5I, FokI     Female Climent et al. [1999]
196   197 c.590G>A p.Gly197Glu       Female Tuchman et al. [1998]
197   198 c.593A>T p.Asn198Ile BinI, BsaBI, BstKTI, DpnI, MboI     Neonatal Yamaguchi et al. [2006]
198   198 c.594C>A p.Asn198Lys       Female Popowska et al. [1999]
199   199 c.595A>G p.Asn199Asp EcoRV     Female Yamaguchi et al. [2006]
200   199 c.596A>G p.Asn199Ser BciVI, HpyCH4III     Neonatal Tuchman et al. [2002]
201   199-200 c.(597_598)delTA Frameshift       Neonatal Tuchman et al. [1994b]
202   201 c.602T>C p.Leu201Pro BsgI, FauI     Neonatal Shimadzu et al. [1998]
203   202 c.604C>T p.His202Tyr RsaI, TatI, [49%]   Late Tuchman et al. [1997]
204   202 c.605A>C p.His202Pro BsgI, MnlI     Female Staudt et al. [1998]
205   203 c.608C>G p.Ser203Cys BtsI, TspRI     Female Tuchman et al. [1994a]
206   205 c.613A>G p.Met205Val BspHI, NlaIII     Neonatal Genet et al. [2000]
207   206 c.617T>G p.Met206Arg MnlI, MslI     Neonatal Tuchman et al. [1997]
208   206 c.618G>C p.Met206Ile BclI, BstKTI, DpnI, MboI, MslI     Female Climent and Rubio [2002b]
209   207 c.620G>A p.Ser207Asn CfoI, HhaI, Hin6I, TspDTI     Neonatal Yamaguchi et al. [2006]
210   207 c.621C>A p.Ser207Arg CfoI, HhaI, Hin6I, TspDTI     Neonatal Shimadzu et al. [1998]
211   208 c.622G>A p.Ala208Thr CfoI, HhaI, Hin6I, ItaI (4%) CpG dinucleotide Late van Diggelen et al. [1996]
212   209 c.626C>T p.Ala209Val BtsI, TseI (1%) [1.4%]   Neonatal Garcia-Perez et al. [1995]
213   210 c.628A>C p.Lys210Gln ApoI, CfoI, HhaI, Hin6I (0%)   Female Valik et al. [2004]
214   213 c.637T>A p.Met213Lys BsmI, HpyCH4V     Female Oppliger Leibundgut et al. [1997]
215   214 c.640C>T p.His214Tyr BsmI, RsaI     Neonatal Yoo et al. [1996]
216   215 c.643C>T p.Leu215Phe   (17%)   Female Ueta et al. [2001]
217   215-216 c.645_646insT Frameshift Eco57I     Neonatal Tuchman et al. [1994a]
218   216 c.646C>G p.Gln216Glu MnlI, SmlI     Neonatal Grompe et al. [1989]
219   217 c.650C>A p.Ala217Glu BbvI, Fnu4HI, Hpy178III, TseI     Female Yamaguchi et al. [2006]
220   220 c.658C>G p.Pro220Ala BslI, MwoI (35%)   Late Oppliger Leibundgut et al. [1996b]
221   220 c.659C>T p.Pro220Leu BslI   Neonatal Yamaguchi et al. [2006]
222   221 c.663G>C p.Lys221Asn MaeII, TaiI     Neonatal Yamaguchi et al. [2006]
223   221 c.663G>A p.Lys221Lys   (8%) Donor splice site error Late Shimadzu et al. [1998]
224 Intron 6   c.663+1G>A       Donor splice site error Female Tuchman et al. [1997]
225     c.663+1G>T       Donor splice site error Female Oppliger Leibundgut et al. [1996a]
226     c.663+2T>C       Donor splice site error Neonatal Tuchman et al. [1997]
227     c.663+2dupT   BslI   Donor splice site error Female Tuchman and Plante [1995]
228     c.664-1G>A   EcoNI, MseI   Acceptor splice site error Neonatal Tuchman et al. [2002]
229     c.664-1delG Frameshift       Female Tuchman et al. [1997]
230 Exon 7   delExon 7-8         Neonatal Suess et al. [1992]
231     delExon 7-9       Somatic mosaicism Late Legius et al. [1990]
232   225 c.673C>A p.Pro225Thr CviJI, MspI [42%]   Late Tuchman et al. [1994b]
233   225 c.674C>G p.Pro225Arg FauI, MspI (0%) Undetectable protein in liver Neonatal Garcia-Perez et al. [1997]
234   225 c.674C>T p.Pro225Leu AluI, MspI (0%) [0.45%]   Neonatal Hentzen et al. [1991]
235   233 c.698C>T p.Ala233Val       Neonatal Yamaguchi et al. [2006]
236   234 c.700G>T p.Glu234X     Neonatal Yamaguchi et al. [2006]
237   239 c.716A>T p.Glu239Val MnlI   Neonatal Yamaguchi et al. [2006]
238   239 c.716A>G p.Glu239Gly BplI, MnlI     Late Yamaguchi et al. [2006]
239   239 c.717G>C p.Glu239Asp Hin4I, MaeII, TaiI     Female Yamaguchi et al. [2006]
240   239 c.717G>A p.Glu239Glu MnlI   Donor splice site error Female Tuchman et al. [1997]
241 Intron 7   c.717+1G>T   MnlI   Donor splice site error Female Tuchman et al. [2002]
242     c.717+1G>A   MnlI   Donor splice site error Neonatal Genet et al. [2000]
243     c.717+2T>C   BglI, SphI   Donor splice site error, skipping exon 7 Neonatal Carstens et al. [1991]
244     c.717+3A>G   BsiHKAI, Bsp1286I   Donor splice site error, skipping exon 7 Neonatal Carstens et al. [1991]
245     c.717+7_22delTCTTTACATGTAAAGC   NlaIII, NspI (0-1.5%) Donor splice site error Neonatal Calvas et al. [1998]
246     c.718-2A>G   BfaI, MaeI   Donor splice site error Female Popowska et al. [1999]
247 Exon 8   c.718-4_729delCTAGAATGGTACCAAG   Acc65I, BfaI, Csp6I, HgiCI, KpnI, MaeI, NlaIV, RsaI   Eliminates an acceptor splice site Female Yamaguchi et al. [2006]
248   242 c.725C>T p.Thr242Ile BanI, KpnI     Late Tuchman et al. [1997]
249   244 c.731T>A p.Leu244Gln AluI, CviJI (8%)   Late Calvas et al. [1998]
250   247 c.740C>A p.Thr247Lys   (0%)   Neonatal Tuchman and Plante [1995]
251   244-247 c.731_739delTGTTGCTGA   AluI     Female Calvas et al. [1998]
252   253 c.757G>A p.Ala253Thr       Neonatal Yamaguchi et al. [2006]
253   253 c.757G>C p.Ala253Pro NlaIV     Neonatal Yamaguchi et al. [2006]
254   253 c.759delA Frameshift BbvI, BsePI, Cac8I, FnuDII, Fnu4HI, TseI     Neonatal Yamaguchi et al. [2006]
255   255 c.764A>C p.His255Pro BpmI, NlaIII     Female Tuchman et al. [1998]
256   260 c.779T>C p.Leu260Ser       Female Yamaguchi et al. [2006]
257   262 c.785C>A p.Thr262Lys PacI (26%) Somatic mosaicism Late Giorgi et al. [2000]
258   262 c.785C>T p.Thr262Ile     History not known Late Yamaguchi et al. [2006]
259   263 c.787G>A p.Asp263Asn       Female Tuchman et al. [1997]
260   263 c.788A>G p.Asp263Gly       Female Tuchman et al. [1998]
261   264 c.790A>G p.Thr264Ala HgaI (22%)   Late Matsuura et al. [1993]
262   264 c.791C>A p.Thr264Asn MfeI, TspEI     Not reported Hwu et al. [2003]
263   264 c.791C>T p.Thr264Ile       Late Shimadzu et al. [1998]
264   265 c.793T>C p.Trp265Arg Hpy1881     Late Yamaguchi et al. [2006]
265   265 c.794G>T p.Trp265Leu   (56%) pH variant Late Giorgi et al. [2000]
266   265 c.795G>A p.Trp265X       Neonatal Yamaguchi et al. [2006]
267   267 c.799A>C p.Ser267Arg BciVI     Female Shimadzu et al. [1998]
268   268 c.803T>C p.Met268Thr NlaIII (6.7%)    Late Matsuura et al. [1993]
269   269 c.806G>A p.Gly269Glu BsmFI (2%)   Neonatal Zimmer et al. [1995]
270   270 c.808C>T p.Gln270X BsmFI     Neonatal McCullough et al. [2000]
271   270 c.809A>C p.Gln270Pro AsuI, AvaII, NlaIV     Female Yamaguchi et al. [2006]
272   271-272 c.810_811delAGinsC Frameshift       Neonatal Khoo et al. [1999]
273   272-273 c.817_819delGAG p.Glu273del BseRI, MnlI (5%)   Late Segues et al. [1996]
274   273 c.818delA Frameshift BseRI     Neonatal Yamaguchi et al. [2006]
275   277 c.829C>T p.Arg277Trp AciI, Fnu4HI, ItaI (5%) [59%] CpG dinucleotide, increased Km for ornithine Late Finkelstein et al. [1990a]
276   277 c.830G>A p.Arg277Gln AciI, AluI, NlaIV (7%) CpG dinucleotide, increased Km for ornithine Late Tuchman et al. [1994b]
277   277 c.830G>T p.Arg277Leu AciI, TseI      Late Tuchman et al. [2002]
278   279 c.835C>T p.Gln279X ApyI, MvaI     Neonatal Tuchman et al. [2002]
279   289 c.867G>T p.Lys289Asn BsrGI, TatI (0%) Possible donor splice site error Neonatal Tuchman et al. [2002]
280 Intron 8   c.867+1G>A   Csp6I, MboII, RsaI   Donor splice site error Neonatal Tuchman et al. [1998]
281     c.867+1G>T   Csp6I, MaeIII, RsaI   Donor splice site error Neonatal Oppliger Leibundgut et al. [1996a]
282     delExon 9         Neonatal Suess et al. [1992]
283 Exon 9 292 c.875delA Frameshift DdeI, MwoI     Neonatal Yamaguchi et al. [2006]
284   294 c.882delT Frameshift CfoI, HinP1I     Neonatal Reish et al. [1993]
285   297-298 c.889_892delGACT Frameshift BsrI, BsiYI, Hpy178III, Hpy188I, (0%)   Neonatal Yamanouchi et al. [2002]
286   298 c.892_893delTG Frameshift BslI, BsrI     Female Schimanski et al. [1996]
287   298 c.893G>C p.Trp298Ser BsiYI, BsrI, HinfI, MlyI, PleI, TaqI (0%)   Neonatal Ensenauer et al. [2005]
288   301 c.903A>T p.Leu301Phe   (3%)   Late Climent and Rubio [2002b]
289   302 c.904C>T p.His302Tyr BtsI, TspRI (0%)   Neonatal Oppliger Leibundgut et al. [1996b]
290   302 c.905A>G p.His302Arg BbvI, BtsI, TseI, TspRI     Neonatal Genet et al. [2000]
291   302 c.905A>T p.His302Leu BtsI, TspRI     Female Gilbert-Dussadier et al. [1996]
292   302 c.906C>G p.His302Gln BtsI, HpyCH4III     Late Tuchman et al. [1997]
293   302 c.906delC Frameshift       Female Yamaguchi et al. [2006]
294   303 c.907T>C p.Cys303Arg AciI, BtsI, TspRI   Ornithine binding site Neonatal Calvas et al. [1998]
295   303 c.907T>G p.Cys303Gly BtsI, CviJI, TspRI   Ornithine binding site Neonatal Tuchman et al. [2002]
296   303 c.908G>A p.Cys303Tyr BtsI, TspRI   Ornithine binding site Female Tuchman et al. [1997]
297   304 c.912G>T p.Leu304Phe Cac8I, MwoI (6%) [74%] Ornithine binding site Late Tuchman et al. [1992]
298   305 c.914C>G p.Pro305Arg       Neonatal Yamaguchi et al. [2006]
299   305 c.914C>A p.Pro305His HpyCH4V     Female Climent and Rubio [2002b]
300   309-310 c.(925-927)delGAA p.Glu309del MboII     Late Tuchman et al. [1994b]
301   310 c.928G>T p.Glu310X MboII     Neonatal Reish et al. [1993]
302   310 c.929A>G p.Glu310Gly MboII     Late Yamaguchi et al. [2006]
303   311 c.931G>A p.Val311Met       Late Yamaguchi et al. [2006]
304   314 c.940_942delGAA p.Glu314del       Female Yamaguchi et al. [2006]
305   315 c.943G>T p.Val315Phe ApoI, EcoRI, TspEI     Female Yamaguchi et al. [2006]
306   315 c.944T>A p.Val315Asp BbsI, MboII     Female Tuchman et al. [2002]
307   315 c.944T>G p.Val315Gly CviJI     Female Tuchman et al. [2002]
308   316 c.947T>C p.Phe316Ser BsmAI     Female Tuchman et al. [2002]
309   318 c.953C>T p.Ser318Phe BseRI     Female Genet et al. [2000]
310   320 c.958C>T p.Arg320X BclI, TaqI (10-15%)   Neonatal Yoo et al. [1996]
311   320 c.959G>T p.Arg320Leu DpnI, TaqI [3.9%] CpG dinucleotide Neonatal Grompe et al. [1991]
312   321 c.962C>A p.Ser321X DpnI, MboI     Neonatal Tuchman et al. [2002]
313   326 c.976G>A p.Glu326Lys MnlI     Female Popowska et al. [1999]
314   328 c.982G>T p.Glu328X       Neonatal Yamaguchi et al. [2006]
315   330 c.[988A>T; 989_990delGA] Frameshift DdeI   Termination of translation Female Climent and Rubio [2002b]
316   330 c.988A>G p.Arg330Gly       Female Tuchman et al. [1997]
317   331 c.991A>T p.Lys331X       Female Yamaguchi et al. [2006]
318   332 c.994T>A p.Trp332Arg Hpy8I, MnlI (0%)   Neonatal Rapp et al. [2001]
319   332 c.995G>A p.Trp332X AccI     Neonatal Yamaguchi et al. [2006]
320   332 c.996G>A p.Trp332X       Neonatal Matsuura et al. [1994]
321   335 c.1005G>A p.Met335Ile NlaIII     Neonatal Tuchman et al. [2002]
322 Intron 9   c.1005+1G>T   MseI   Donor splice site error Neonatal Tuchman et al. [1997]
323     c.1005+2T>C   Cac8I   Donor splice site error Neonatal Tuchman et al. [2002]
324     c.1006-3C>G   BspHI, MnlI (2.7%) Acceptor splice site error Late Climent and Rubio [2002b]
325     c.1006-1G>A   AluI [23%] Acceptor splice site error Neonatal Gyato et al. [2004]
326 Exon 10 336 c.1006G>T p.Ala336Ser CviJI     Late Tuchman et al. [1998]
327   337 c.1009G>C p.Val337Leu   (<5%)   Late Rohininath et al.[2004]; Matsuda and Tanase [1997]
328   339 c.1015G>C p.Val339Leu MwoI     Neonatal Tuchman et al. [1997]
329   340 c.1018T>C p.Ser340Pro BanI, BsmFI     Female Oppliger Leibundgut et al. [1997]
330   341 c.1022T>C p.Leu341Pro AciI, FauI     Female Climent and Rubio [2002b]
331   343 c.1028C>A p.Thr343Lys       Female Tuchman and Plante [1995]
332   345 c.1033T>C p.Tyr345His       Late Yamaguchi et al. [2006]
333   345 c.1033T>G p.Tyr345Asp HinfI, PleI     Female Tuchman et al. [1992]
334   345 c.1034A>G p.Tyr345Cys       Neonatal Tuchman et al. [1998]
335   347 c.1039C>A p.Pro347Thr BbvCI, Bpu10I, BsaXI, HphI, MnlI     Female Yamaguchi et al. [2006]
336   348 c.1042C>T p.Gln348X BbvCI, MnlI     Female Oppliger Leibundgut et al. [1997]
337   354 c.1061T>G p.Phe354Cys ApoI, Tsp509I (1.8%)   Late Myers and Shook [1996]
338     delExon 1-9         Neonatal Yamaguchi et al. [2006]
339     delExon 9         Female Yamaguchi et al. [2006]
340     delExon 1-8         Neonatal Yamaguchi et al. [2006]
341     delExon 2-4         Female Yamaguchi et al. [2006]
The CP and ornithine binding sites were identified from the crystal structure. CpG dinucleotides and splice site mutations were identified by bioinformatic analysis.
a nucleotide +1is the A of the ATG-translation initiation codon of RefSeq NM_000531.3
b For deletions or insertions, the cDNA nucleotide number is given starting with the A of the initiation ATG as nucleotide number 1.
c Endonuclease recognition site
d (%) Residual enzyme activity in liver or intestine or by expression studies, [15N] residual ammonium nitrogen incorporation into urea
e Neonatal (hyperammonemia within the first week of life, severe phenotype). Late (late onset, milder phenotype)
f First report of the mutation