l-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1
Open accessAbstract
l-2-Hydroxyglutaric aciduria (l-2-HGA) is characterized by progressive deterioration of central nervous system function including epilepsy and macrocephaly in 50% of cases, and elevated levels of l-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). Nuclear magnetic resonance imaging shows distinct abnormalities. We report the identification of a gene for l-2-HGA aciduria (MIM 236792) using homozygosity mapping. Nine homozygous mutations including three missense mutations, two nonsense mutations, two splice site mutations and two deletions were identified in the gene C14orf160, localized on chromosome 14q22.1, in 21 patients from one non-consanguineous and 14 consanguineous Turkish families. We propose to name the gene duranin. Duranin encodes a putative mitochondrial protein with homology to FAD-dependent oxidoreductases. The functional role of this enzyme in intermediary metabolism in humans remains to be established.
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D-2-HG occupies the active site of histone demethylases, increasing histone methylation in primary gliomas.
“D-2-HG produced by mIDH1/2 has been shown to drive a CpG island methylator phenotype (G-CIMP) in both glioma and ICC tumours to promote tumorigenesis, and has also been found to occupy the active site of histone demethylases thereby increasing histone methylation in primary gliomas121,123-125.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [125]
D-2-HG produced by mIDH1/2 drives a CpG island methylator phenotype in glioma and ICC tumours to promote tumorigenesis.
“D-2-HG produced by mIDH1/2 has been shown to drive a CpG island methylator phenotype (G-CIMP) in both glioma and ICC tumours to promote tumorigenesis, and has also been found to occupy the active site of histone demethylases thereby increasing histone methylation in primary gliomas121,123-125.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [125]
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Primer3 on the WWW for General Users and for Biologist Programmers
Rozen, S., & Skaletsky, H. (2003) · Humana Press eBooks · doi:10.1385/1-59259-192-2:365 · Cited by 14,952 · see citing works
Beighton, P., & Beighton, G. (1997) · Springer eBooks · doi:10.1007/978-1-4471-0925-9_118 · Cited by 3,165 · see citing works
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060 · see citing works
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences
Mammalian Gene Collection (MGC) Program Team* (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242603899 · Cited by 1,742 · see citing works
Easy calculations of lod scores and genetic risks on small computers.
Lathrop, M. G., & Lalouel, J.-M. (1984) · PubMed · Cited by 1,533 · see citing works
Self-citationComplete sequencing and characterization of 21,243 full-length human cDNAs
Ota, T., Suzuki, Y., Nishikawa, T., Otsuki, T., Sugiyama, T., Irie, R., Wakamatsu, A., Hayashi, K., Sato, H., Nagai, K., et al. (2004) · Nature Genetics · doi:10.1038/ng1285 · Cited by 925 · see citing works
Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland
Hästbacka, J., de la Chapelle, A., Kaitila, I., Sistonen, P., Weaver, A., & Lander, E. (1992) · Nature Genetics · doi:10.1038/ng1192-204 · Cited by 558 · see citing works
L‐2‐Hydroxyglutaric aciduria: an inborn error of metabolism?
Duran, M., Kamerling, J. P., Bakker, H. D., van Gennip, A. H., & Wadman, S. K. (1980) · Journal of Inherited Metabolic Disease · doi:10.1007/bf02312543 · Cited by 226 · see citing works
Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease
Kaul, R., Ping Gao, G., Balamurugan, K., & Matalon, R. (1993) · Nature Genetics · doi:10.1038/ng1093-118 · Cited by 221 · see citing works
Physiology and pathophysiology of organic acids in cerebrospinal fluid
Hoffmann, G. F., Meier‐Augenstein, W., Stöckler, S., Surtees, R. A. H., Rating, D., & Nyhan, W. L. (1993) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711898 · Cited by 191 · see citing works
L ‐2‐hydroxyglutaric acidemia: A novel inherited neurometabolic disease
Barth, P. G., Hoffmann, G. F., Jaeken, J., Lehnert, W., Hanefeld, F. A., Gennip, A. H., Durán, M., Valk, J., Schutgens, R. B. H., Trefz, F. K., et al. (1992) · Annals of Neurology · doi:10.1002/ana.410320111 · Cited by 153 · see citing works
Gibson, K. M., ten Brink, H. J., Schor, D. S. M., Kok, R. M., Bootsma, A. H., Hoffmann, G. F., & Jakobs, C. (1993) · Pediatric Research · doi:10.1203/00006450-199309000-00007 · Cited by 121 · see citing works
Barth, P. G., Hoffmann, G. F., Jaeken, J., Wanders, R. J. A., Durán, M., Jansen, G. A., Jakobs, C., Lehnert, W., Hanefeld, F. A., Valk, J., et al. (1993) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711907 · Cited by 96 · see citing works
Self-citationTopical Review Article: Organic Acidurias: A Review. Part 1
Ozand, P. T., & Gascon, G. G. (1991) · Journal of Child Neurology · doi:10.1177/088307389100600302 · Cited by 89 · see citing works
Barbot, C., Fineza, I., Diogo, L. M., Maria, M., Melo, J., ̃es, A. G., Pires, M. M., Cardoso, M. L., & Vilarinho, L. (1997) · Brain and Development · doi:10.1016/s0387-7604(97)00574-3 · Cited by 86 · see citing works
Fischer, J., Faure, A., Bouadjar, B., Blanchet‐Bardon, C., Karaduman, A., Thomas, I., Emre, S. D., Cure, S., Özgüç, M., Weissenbach, J., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/302814 · Cited by 81 · see citing works
Self-citationChen, E., Nyhan, W. L., Jakobs, C., Greco, C. M., Barkovich, A. J., Cox, V., & Packman, S. (1995) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01799264 · Cited by 70 · see citing works
L-2-hydroxyglutaric aciduria: a report of 29 patients
Topçu, M., Aydin, Ö. F., Yalçınkaya, C., Haliloğlu, G., Aysun, S., Anlar, B., Topaloğlu, H., Turanlı, G., Yalnızoğlu, D., Kesımer, M., et al. (2005) · The Turkish Journal of Pediatrics · doi:10.24953/turkjpediatr.2005.2673 · Cited by 62 · see citing works
Self-citationL-2-Hydroxyglutaric aciduria: MRI in seven cases
D’Incerti, L., Farina, L., Moroni, I., Uziel, G., & Savoiardo, M. (1998) · Neuroradiology · doi:10.1007/s002340050673 · Cited by 60 · see citing works
Clinical, biochemical and neuroradiological findings in L -2-hydroxyglutaric aciduria
Moroni, I., D’Incerti, L., Farina, L. M., Rimoldi, M., & Uziel, G. (2000) · Neurological Sciences · doi:10.1007/s100720070104 · Cited by 58 · see citing works
Rashed, M. S., Al‐Amoudi, M., & Aboul-Enein, H. Y. (2000) · Biomedical Chromatography · doi:10.1002/1099-0801(200008)14:5 · Cited by 53 · see citing works
Topçu, M., Erdem, G., Saatçi, I., Aktan, G., Simsek, A., Renda, Y., Schutgens, R. B. H., Wanders, R. J. A., & Jacobs, C. (1996) · Journal of Child Neurology · doi:10.1177/088307389601100505 · Cited by 50 · see citing works
Self-citationl ‐2‐Hydroxyglutaric aciduria: Three Australian cases
Wilcken, B. M., Pitt, J. J., Heath, D., Walsh, P., Wilson, G., & Buchanan, N. (1993) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711665 · Cited by 48 · see citing works
Topical Review Article: Organic Acidurias: A Review Part 2
Ozand, P. T., & Gascon, G. G. (1991) · Journal of Child Neurology · doi:10.1177/088307389100600402 · Cited by 48 · see citing works
Clinical and pathological study of three Tunisian siblings with L-2-hydroxyglutaric aciduria
Larnaout, A., Hentati, F., Belal, S., Hamida, C. B., Hamida, M. B., & Kaabachi, N. (1994) · Acta Neuropathologica · doi:10.1007/bf00310381 · Cited by 46 · see citing works
Hanefeld, F. A., Kruse, B., Bruhn, H., & Frahm, J. (1994) · Pediatric Research · doi:10.1203/00006450-199405000-00015 · Cited by 39 · see citing works
l -2-Hydroxyglutaric aciduria: two Japanese adult cases in one family
Fujitake, J., Ishikawa, Y., Fujii, H., Nishimura, K., Hayakawa, K., Inoue, F., Terada, N., Okochi, M., & Tatsuoka, Y. (1999) · Journal of Neurology · doi:10.1007/s004150050367 · Cited by 39 · see citing works
Plasma Lysine Concentration and Availability of 2‐Ketoglutarate in Liver Mitochondria
Kamoun, P., Richard, V., Rabier, D., & Saudubray, J. (2002) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1015195009330 · Cited by 36 · see citing works
Organic acids in cerebrospinal fluid and plasma of patients with l ‐2‐hydroxyglutaric aciduria
Hoffmann, G. F., Jakobs, C., Holmes, B., Mitchell, L., Becker, G., Hartung, H., & Nyhan, W. L. (1995) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711763 · Cited by 32 · see citing works
l ‐2‐Hydroxyglutaric aciduria: Two further cases
Divry, P., Jakobs, C., Vianey‐Saban, C., Gibson, K. M., Michelakakis, H., Papadimitriou, A., Divari, R., Chabrol, B., Cournelle, M., & Livet, M.-O. (1993) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711666 · Cited by 31 · see citing works
Jansen, G. A., & Wanders, R. J. A. (1993) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(93)90121-g · Cited by 30 · see citing works
Self-citationL-2-Hydroxyglutaric Aciduria: Clinical Heterogeneity Versus Biochemical Homogeneity in a Sibship
Klerk, J. D., Huijmans, J. G. M., Stroink, H., Robben, S. G. F., Jakobs, C., & Durán, M. (1997) · Neuropediatrics · doi:10.1055/s-2007-973722 · Cited by 26 · see citing works
L‐2‐Hydroxyglutaric aciduria and lactic acidosis
Barth, P. G., Wanders, R. J. A., Scholte, H. R., Abeling, N. G. G. M., Jakobs, C., Schutgens, R. B. H., & Vreken, P. (1998) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005316121584 · Cited by 24 · see citing works
Self-citationWanders, R. J. A., Vilarinho, L., Hartung, H., Hoffmann, G. F., Mooijer, P. A. W., Jansen, G. A., Huijmans, J. G. M., de Klerk, J. B. C., ten Brink, H. J., Jakobs, C., et al. (1997) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005355316599 · Cited by 23 · see citing works
Self-citationStruys, E. A., Verhoeven‐Duif, N. M., Roos, B., & Jakobs, C. (2003) · Clinical Chemistry · doi:10.1373/49.7.1133 · Cited by 21 · see citing works
l-2-hydroxyglutaric aciduria in two siblings
Sztriha, L., Gururaj, A., Vreken, P., Nork, M., & Lestringant, G. G. (2002) · Pediatric Neurology · doi:10.1016/s0887-8994(02)00405-8 · Cited by 18 · see citing works
Macrocephaly as the presenting feature of l ‐2‐hydroxyglutaric aciduria in a 5‐month‐old boy
Diogo, L. M., Fineza, I., Canha, J., Borges, L., Cardoso, M. L., & Vilarinho, L. (1996) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01799270 · Cited by 16 · see citing works
L-2-Hydroxyglutaric aciduria presenting as status epilepticus
Zafeiriou, D., Sewell, A., Savvopoulou-Augoustidou, P. A., Gombakis, N., & Katzos, G. S. (2001) · Brain and Development · doi:10.1016/s0387-7604(01)00206-6 · Cited by 15 · see citing works
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Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875 · see citing works
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Oldham, W. M., Clish, C. B., Yang, Y., & Loscalzo, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.021 · Cited by 364 · see citing works
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Latini, A., da Silva, C. G., Ferreira, G. C., Schuck, P. F., Scussiato, K., Sarkis, J. J., Dutra Filho, C. S., Wyse, A. T. S., Wannmacher, C. M. D., & Wajner, M. (2005) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2005.05.002 · Cited by 88 · see citing works
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Ma, S., Jiang, B., Deng, W., Gu, Z.-K., Wu, F.-Z., Li, T., Xia, Y., Yang, H., Ye, D., Xiong, Y., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3330 · Cited by 55 · see citing works
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Vilarinho, L., Cardoso, M. L., Gaspar, P., Barbot, C., Azevedo, L., Diogo, L. M., dos Santos, M. L. B. M., Carrilho, I., Fineza, I., Kok, F., et al. (2005) · Human Mutation · doi:10.1002/humu.9373 · Cited by 43 · see citing works
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Ma, S., Sun, R., Jiang, B., Gao, J., Deng, W., Liu, P., He, R., Cui, J., Ji, M., Yi, W., et al. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00492-16 · Cited by 39 · see citing works
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Struys, E. A., Gibson, K. M., & Jakobs, C. (2007) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-007-0697-5 · Cited by 30 · see citing works
Wilms Tumor in a Child with L-2-hydroxyglutaric Aciduria
Rogers, R. E., DeBerardinis, R. J., Klesse, L. J., Boriack, R. L., Margraf, L. R., & Rakheja, D. (2010) · Pediatric and Developmental Pathology · doi:10.2350/09-12-0768-cr.1 · Cited by 29 · see citing works
Hüdig, M., Maier, A., Scherrers, I., Seidel, L., Jansen, E. E. W., Mettler‐Altmann, T., Engqvist, M. K. M., & Maurino, V. G. (2015) · Plant and Cell Physiology · doi:10.1093/pcp/pcv108 · Cited by 27 · see citing works
L ‐2‐Hydroxyglutaric aciduria: Identification of ten novel mutations in theL2HGDHgene
Sass, J. O., Jobard, F., Topçu, M., Mahfoud, A., Werlé, E., Cure, S., Al-Sannaa, N. A., AlShahwan, S., Bataillard, M., Cimbalistienė, L., et al. (2008) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-008-0855-4 · Cited by 27 · see citing works
Self-citationRibeiro, R. T., Zanatta, Â., Amaral, A. U., Leipnitz, G., de Oliveira, F. H., Seminotti, B., & Wajner, M. (2018) · Neurotoxicity Research · doi:10.1007/s12640-018-9874-6 · Cited by 24 · see citing works
Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in Arab kindreds
Faiyaz‐Ul‐Haque, M., Alsayed, M. D., Faqeih, E., Jamil, M., Saeed, A., Amoudi, M. S., Kaya, N., Abalkhail, H. A., Al-Abdullatif, A., Rashed, M. S., et al. (2014) · Annals of Saudi Medicine · doi:10.5144/0256-4947.2014.107 · Cited by 23 · see citing works
The role of mutation of metabolism-related genes in genomic hypermethylation
Waterfall, J. J., Killian, J. K., & Meltzer, P. S. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.08.003 · Cited by 23 · see citing works
Tunisian Network on Mental Retardation study, Jellouli, N. K., Salem, I. H., Ellouz, E., Kamoun, F., kamoun, F., Tlili, A., Kaabachi, N., Triki, C., & Fakhfakh, F. (2014) · Journal of Human Genetics · doi:10.1038/jhg.2014.4 · Cited by 22 · see citing works
Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism
Hoffmann, G. F., & Kölker, S. (2016) · Springer eBooks · doi:10.1007/978-3-662-49771-5_22 · Cited by 22 · see citing works
L-2-hydroxyglutaric aciduria – review of literature and case series
Ahmed, S., Siddiqui, A., DeBerardinis, R. J., Ni, M., Gu, W., Cai, F., Vu, H., & Afroze, B. (2023) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000000326 · Cited by 18 · see citing works
L-2-hydroxyglutaric Aciduria in Two Female Yorkshire Terriers
Sánchez‐Masián, D., Artuch, R., Mascort, J., Jakobs, C., Salomons, G. S., Zamora, A., Casado, M., Fernandez, M., Recio, A., & Feliu‐Pascual, A. L. (2012) · Journal of the American Animal Hospital Association · doi:10.5326/jaaha-ms-5967 · Cited by 17 · see citing works
Farias, F. H., Zeng, R., Johnson, G. S., Shelton, G. D., Paquette, D., & O’Brien, D. P. (2012) · BMC Veterinary Research · doi:10.1186/1746-6148-8-124 · Cited by 15 · see citing works
Hemiconvulsion-Hemiplegia-Epilepsy Syndrome as a Presenting Feature of L-2-Hydroxyglutaric Aciduria
Lee, C., Born, M. L., Salomons, G. S., Jakobs, C., & Woelfle, J. (2006) · Journal of Child Neurology · doi:10.1177/08830738060210061601 · Cited by 15 · see citing works
L-2-Hydroxyglutaric Aciduria and Brain Tumors
Yazıcı, N., Sarıalioğlu, F., Alkan, Ö., Kayaselçuk, F., & Erol, İ. (2009) · Journal of Pediatric Hematology/Oncology · doi:10.1097/mph.0b013e3181b258c6 · Cited by 15 · see citing works
Yang, J., Chen, X., Jin, S., & Ding, J. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105491 · Cited by 14 · see citing works
Sahm, F., Capper, D., Meyer, J., Hartmann, C. J., Herpel, E., Andrulis, M., Mechtersheimer, G., Petersen, I., Paulus, W., & von Deimling, A. (2011) · Histopathology · doi:10.1111/j.1365-2559.2011.03823.x · Cited by 13 · see citing works
Neuropathological Findings in a Staffordshire Bull Terrier with l-2-Hydroxyglutaric Aciduria
Scurrell, E. J., Davies, E. S., Baines, E. A., Cherubini, G. B., Platt, S. R., Blakemore, W. F., Williams, A., & Schöniger, S. (2008) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2007.11.005 · Cited by 13 · see citing works
Muthusamy, K., Sudhakar, S. V., Christudass, C. S., Chandran, M., Thomas, M. M., & Gibikote, S. (2019) · Journal of Clinical Imaging Science · doi:10.25259/jcis-9-3 · Cited by 14 · see citing works
Muzammal, M., Ali, M., Brugger, B. A., Blatterer, J., Ahmad, S., Taj, S., Shah, S. K., Khan, S., Enzinger, C., Petek, E., et al. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00832-2 · Cited by 13 · see citing works
L-2-hydroxyglutaric aciduria: A case report
Jovic, N., Kosać, A., & Koprivšek, K. (2014) · Srpski arhiv za celokupno lekarstvo · doi:10.2298/sarh1406337j · Cited by 12 · see citing works
Larnaout, A., Amouri, R., Kéfi, M., & Hentati, F. (2008) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-008-0934-6 · Cited by 12 · see citing works
Cansever, M. Ş., Zübarioğlu, T., Oruç, Ç., Kıykım, E., Gezdirici, A., Neşeli̇oğlu, S., Erel, Ö., Yalçınkaya, C., & Zeybek, A. Ç. A. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0354-8 · Cited by 11 · see citing works
Muzammal, M., Cerbo, A. D., Almusalami, E. M., Farid, A., Khan, M. A., Ghazanfar, S., Mohaini, M. A., Alsalman, A. J., Alhashem, Y. N., Hawaj, M. A. A., et al. (2022) · Genes · doi:10.3390/genes13040698 · Cited by 14 · see citing works
A novel mutation as a cause of L-2-hydroxyglutaric aciduria
O’Connor, G., King, M. D., Salomons, G. S., Jakobs, C., & Hardiman, O. M. (2009) · Journal of Neurology · doi:10.1007/s00415-009-0107-z · Cited by 11 · see citing works
Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report
Ullah, M. I., Nasır, A., Ahmad, A., Harlalka, G. V., Ahmad, W., Hassan, M. J., Baple, E. L., Crosby, A. H., & Chioza, B. A. (2018) · BMC Medical Genetics · doi:10.1186/s12881-018-0532-x · Cited by 10 · see citing works
Measurement of Oncometabolites d-2-Hydroxyglutaric Acid and l-2-Hydroxyglutaric Acid
Jones, P. M., Boriack, R. L., Struys, E. A., & Rakheja, D. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7142-8_14 · Cited by 10 · see citing works
Álvarez-González, E., & Sierra, L. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25169054 · Cited by 10 · see citing works
Findings on serial MRI in a childhood case of L2-hydroxyglutaric aciduria
Kular, S. (2019) · Radiology Case Reports · doi:10.1016/j.radcr.2019.09.035 · Cited by 9 · see citing works
Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria
Peng, W., Ma, X., Yang, X. F., Zhang, W., Yan, L., Wang, Y., Liu, X., Wang, Y., & Feng, Z. (2018) · BMC Medical Genetics · doi:10.1186/s12881-018-0675-9 · Cited by 9 · see citing works
Mazzei, R., Ungaro, C., Garreffa, G., Conforti, F. L., Mollo, A., Sprovieri, T., Servillo, P., Blasi, V. D., Gallo, O., Cerasa, A., et al. (2010) · Neurological Sciences · doi:10.1007/s10072-010-0416-0 · Cited by 9 · see citing works
Kranendijk, M., Salomons, G. S., Gibson, K. M., Zeybek, A. Ç. A., Bekri, S., Christensen, E., Clarke, J. T. R., Hahn, A., Korman, S. H., Mejaški‐Bošnjak, V., et al. (2009) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-009-1282-x · Cited by 9 · see citing works
Identification of novel L2HGDH gene mutations and update of the pathological spectrum
Vilarinho, L., Tafulo, S., Sibilio, M., Kok, F., Fontana, F., Diogo, L. M., Venâncio, M., Ferreira, M., Nogueira, C., Valongo, C., et al. (2009) · Journal of Human Genetics · doi:10.1038/jhg.2009.110 · Cited by 8 · see citing works
Intraventricular Glioblastoma Multiforme in A Child with L2-Hydroxyglutaric Aciduria
Tan, A. P., & Mankad, K. (2017) · World Neurosurgery · doi:10.1016/j.wneu.2017.11.106 · Cited by 8 · see citing works
Ribeiro, R. T., Carvalho, A. V. S., Palavro, R., Durán‐Carabali, L. E., Zemniaçak, Â. B., Amaral, A. U., Netto, C. A., & Wajner, M. (2022) · Neurotoxicity Research · doi:10.1007/s12640-022-00625-0 · Cited by 9 · see citing works
Exonic mutations in the L2HGDH gene in Staffordshire bull terriers
Short, A. D., Mellersh, C. S., Platt, H., Carter, S. D., Timofte, D., Lohi, H., & Ollier, W. (2010) · Veterinary Record · doi:10.1136/vr.c4476 · Cited by 8 · see citing works
Fortina, P., Londin, E., Park, J. Y., & Kricka, L. J. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7142-8 · Cited by 7 · see citing works
Epilepsy in a Young Adult Caused by L-2-Hydroxyglutaric Aciduria: A Case Report
Vembu, P., Rudwan, M., Yadav, G., & Khan, R. A. (2008) · Medical Principles and Practice · doi:10.1159/000117804 · Cited by 8 · see citing works
Cerebral neoplasm in L-2-hydroxyglutaric aciduria: two different presentations
Dilber, B., Havalı, C., Eroğlu, N., Aydın, K., Şahin, S., & Cansu, A. (2019) · Child s Nervous System · doi:10.1007/s00381-019-04466-9 · Cited by 7 · see citing works
A 7-year-old boy with hand tremors and a novel mutation for L-2-hydroxyglutaric aciduria
Olgaç, A., Orgun, L. T., Ezgü, F., Biberoğlu, G., & Tümer, L. (2019) · Balkan Journal of Medical Genetics · doi:10.2478/bjmg-2019-0015 · Cited by 8 · see citing works
Cansever, M. Ş., Öztekin, N., Kıykım, E., Zübarioğlu, T., & Zeybek, A. Ç. A. (2023) · Journal of Separation Science · doi:10.1002/jssc.202300145 · Cited by 7 · see citing works
Developmental abnormalities and mental retardation
Topçu, M., & Yalnızoğlu, D. (2013) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52891-9.00021-x · Cited by 6 · see citing works
Self-citationl-2 Hydroxyglutaric aciduria presenting with anxiety symptoms
Gökçen, C., Işıkay, S., & Yılmaz, K. (2013) · BMJ Case Reports · doi:10.1136/bcr-2013-009512 · Cited by 6 · see citing works
Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism
Kölker, S., & Hoffmann, G. F. (2022) · Springer eBooks · doi:10.1007/978-3-662-63123-2_22 · Cited by 6 · see citing works
Zhang, Y., Wang, C., Yang, K., Wang, S., Tian, G., & Chen, Y. (2018) · Neurological Sciences · doi:10.1007/s10072-018-3483-2 · Cited by 6 · see citing works
Movement Disorders and Inherited Metabolic Disorders
(2020) · Cambridge University Press eBooks · doi:10.1017/9781108556767 · Cited by 6 · see citing works
Tracing the Origin of L-2-Hydroxyglutaric Aciduria in a Family
Sass, J. O., Romrell, J., Vinson, S. Y., Fernandez, H. H., Fischer, J., Rodriguez, R. L., & Okun, M. S. (2009) · International Journal of Neuroscience · doi:10.1080/00207450903139655 · Cited by 6 · see citing works
Self-citationMitochondrial l-2-hydroxyglutarate is a physiological signalling metabolite
Chakrabarty, R. P., Vranken, J. G. V., Aoi, Y., Poor, T. A., McElroy, G. S., Vasan, K., Soliman, S. H. A., Iwanaszko, M., Grant, R. A., Howard, B. C., et al. (2026) · Nature · doi:10.1038/s41586-026-10564-x · Cited by 6 · see citing works
L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria
Christen, M., Janzen, N., Fraser, A., Sewell, A., Jagannathan, V., Guevar, J., Leeb, T., & Sánchez‐Masián, D. (2021) · Genes · doi:10.3390/genes12050682 · Cited by 5 · see citing works
L-2 Hydroxyglutaric aciduria presenting with status epilepticus
Işıkay, S. (2013) · BMJ Case Reports · doi:10.1136/bcr-2013-010164 · Cited by 5 · see citing works
Shang, J., Wang, X., Zhang, M., Wang, R., Zhang, C., Huang, H., & Wang, S. (2021) · Applied and Environmental Microbiology · doi:10.1128/aem.02769-20 · Cited by 5 · see citing works
Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism
Hoffmann, G. F., & Kölker, S. (2011) · Springer eBooks · doi:10.1007/978-3-642-15720-2_23 · Cited by 5 · see citing works
Inherited Metabolic Disorders Associated with Extrapyramidal Symptoms
Singer, H. S., Mink, J. W., Gilbert, D. L., & Jankovic, J. J. (2010) · Elsevier eBooks · doi:10.1016/b978-0-7506-9852-8.00015-1 · Cited by 5 · see citing works
Karataş, H., Saygı, S., Baştan, B., Eker, A., Kurşun, O., Ayhan, Y., & Ciğer, A. (2010) · The Neurologist · doi:10.1097/nrl.0b013e31819f9556 · Cited by 5 · see citing works
Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism
Hoffmann, G. F. (2006) · Springer eBooks · doi:10.1007/978-3-540-28785-8_23 · Cited by 5 · see citing works
Kölker, S. (2014) · Encyclopedia of the Neurological Sciences · doi:10.1016/b978-0-12-385157-4.00111-1 · Cited by 5 · see citing works
Clinical, Neuroimaging, and Genetic Features of the Patients with L-2-Hydroxyglutaric Aciduria
Canda, E. E., Köse, M., Yazıcı, H., Er, E., Eraslan, C., Özkınay, F., Çöker, M., Uçar, S. K., Habif, S., Karaca, E., et al. (2018) · The Journal of Pediatric Research · doi:10.4274/jpr.59454 · Cited by 5 · see citing works
- Authors
- Topçu, M., Jobard, F., Halliez, S., Coskun, T., Yalçinkayal, C., Gerceker, F. O., Wanders, R. J. A., Prud'homme, J.-F., Lathrop, M., Özguc, M., & Fischer, J.
- Affiliations
- Hacettepe University (TR)
- Corresponding author
- Topçu, Meral
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-09-22
- Volume
- 13
- Issue
- 22
- Pages
- 2803-2811
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2134258065
- Cited by
- 133
- References
- 38
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 2 · 2015: 4 · 2014: 7 · 2013: 10 · 2012: 11
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Hacettepe University Institutional Repository (hacettepe.edu.tr) (submittedVersion, other-oa)
- Funders
- Türkiye Bilimsel ve Teknolojik Araştırma Kurumu
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- L-2-hydroxyglutaric aciduria, homozygosity mapping, gene identification, missense mutations, nonsense mutation, splice site mutation, deletion, consanguineous family, mitochondrial proteins, FAD-dependent oxidoreductase, epilepsy, macrocephaly
- MeSH terms
- Adolescent, Adult, Alcohol Oxidoreductases, Central Nervous System Diseases, Child, Child, Preschool, Chromosomes, Human, Pair 14, Consanguinity, Female, Glutarates, Humans, Magnetic Resonance Imaging, Male, Molecular Sequence Data, Mutation, Oxidoreductases, Turkey, Linkage Disequilibrium, Mitochondrial Proteins
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