No abstract

Deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier (AGC), encoded by the SLC25A13 gene on chromosome 7q21.3, causes autosomal recessive disorders: adult-onset type II citrullinemia (CTLN2) and neonatal hepatitis associated with intrahepatic cholestasis (NICCD). So far, we have described 12 SLC25A13 mutations: 11 were from Japan and one from Israel. Three mutations found in Chinese and Vietnamese patients were the same as those in Japanese patients. In the present study, we identified a novel mutation IVS6+1G>C in a Japanese CTLN2 patient and widely screened 12 SLC25A13 mutations found in Japanese patients in control individuals from East Asia to confirm our preliminary results that the carrier frequency was high in Asian populations. Mutations 851-854del and 1638-1660dup were found in all Asian countries tested, and 851-854del associated with 290-haplotype in microsatellite marker D7S1812 was especially frequent. Other mutations frequently detected were IVS11+1G>A in Japanese and Korean, S225X in Japanese, and IVS6+5G>A in Chinese populations. We found a remarkable difference in carrier rates in China (including Taiwan) between north (1/ 940) and south (1/48) of the Yangtze River. We detected many carriers in Chinese (64/4169 = 1/65), Japanese (20/1372 = 1/69) and Korean (22/2455 = 1/112) populations, suggesting that over 80,000 East Asians are homozygotes with two mutated SLC25A13 alleles.

The tetrahydride-bridged complex ( C~M~~) R U (~-H )~R U ( C~M~~)(2) is synthesized by the reaction of [(C5Mes)RuCl212 (1) with LiAlH4, which is characterized as a classical hydride complex on the basis of the 2' 1 value and X-ray diffraction study. In the presence of acid, 2 decomposes to form a coordinatively unsaturated species, which is trapped by the 6-electron ligands to yield the cationic Welectron complexes. Treatment of 2 with ethylene yields (C5Me5)-Ru(CsMe5) (9), structural analogue of the intermediate 8. Thermolysis of 6 in toluene at 60 "C under 1 atm of ethylene generates a dinuclear ruthenacyclopentadiene complex ((25- M~~)R~(CHFCH~)(CM~=CHCH=CM~)R~(CSM~~)(10) as a result of the C-C coupling reaction among the coordinated ethylene and two vinyl ligands. The bis(palky1idene) complex (C6Me5)Ru(pL-CHMe) [pCMe(CH=CHCOMe)Ru(C5Me6) (13) which seems to be a model compound of the intermediate of the cyclometalation leading to 10 is obtained upon heating a divinyl complex (C~M~~)RU(CHFCHCOM~)(CH=CH~)~RU(C~M~~) (12) in refluxing toluene. The ethylene molecule coordinated in 10 inserts into the Ru-C bond of the ruthenacyclopentadiene to form (CsMes)Ru(CMe=CHCH=CMeCH=CH2)(p-H)Ru(CsMe5) (16) when 10 is heated in toluene at 110 "C. Regioselective insertion of a,P-unsaturated ketones into the Ru-C bond of the ruthenacycle giving (C5Me5)Ru(CMe=CHCH=CMeCR1=CCOR2) (p-H)Ru(C5Me5) (17, R1 = H, R2 = Me; 18, R1, R2 = (CH2)2; 19, R', R2 = (CH2)3) is demonstrated in the thermolysis of 10 in the presence of methyl vinyl ketone, cyclopentenone, and cyclohexenone. The molecular structures of several of the products are determined by single-crystal X-ray diffraction studies. Crystal data for 2: space group P 2 / a , a = 12.291(2) A, b = 8.521(1) A, c = 10.053(2) A, = 108.52(1)", V = 998.3(3) A3, and Dcdcd = 1.585 g cm3 for Z = 2. Least-squares refinement based on 2391 reflections converged to R = 0.0220 and R, = 0.0220. Crystal data for 6: space group PI, a = 11.335(2) A, b = 14.315(2) A, c = 8.401(2) A, a = 95.09(2)", p = 117,18(1)", y = 94.36(1)", v = 1197.4(6) A3, and D d c d = 1.538 g cm3 for z = 2. Least-squares refinement based on 2621 reflections converged to R = 0.0900 and R, = 0.1581. Crystal data for 9: space group Pbca, a = 17.876(2) A, b = 20.896(2) A, c = 17.690(2) A, V = 6608(1) g cm3, andDcdcd = 1.529 g cm3 for Z = 8. Least-squares refinement based on 2186 reflections converged to R = 0.057 and R, = 0.040. Crystal data for 10: space group P21/n, a = 14.882(2) A, b = 19.718(4) A, c = 8.794(1) A, = 92.30(2)", v = 2578.5(8) A3, and Dcdcd = 1.496 g ~m -~ for z = 4. Least-squares refinement based on 5731 reflections converged to R = 0.044 and R, = 0.041. Crystal data for 13: space group P21/a, a = 17.210(6) A, b = 9.693(6) A, c = 16.037(7) A, p = 100.366(3)", V = 2632(2) A3, andDdcd = 1.506 g ~m -~ for Z = 4. Least-squares refinement based on 3781 reflections converged to R = 0.037 and R, = 0.035. Crystal data for 16: space group E 1 / a , a = 18.814(2) A, b = 9.212(5) A, c = 15.068(5) A, p = 100.31(2)O, V = 2569(2)...