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Chapter 22 - Neurotransmitter Disorders: DNAJC12-Deficient Hyperphenylalaninemia – An Emerging Neurotransmitter Disorder

from Section II - A Metabolism-Based Approach to Movement Disorders and Inherited Metabolic Disorders

Published online by Cambridge University Press:  24 September 2020

By
Nenad Blau  and
Manuel Schiff
Edited by
Darius Ebrahimi-Fakhari  and
Phillip L. Pearl
Darius Ebrahimi-Fakhari
Affiliation:
Harvard Medical School
Phillip L. Pearl
Affiliation:
Harvard Medical School
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Summary

DNAJC12 deficiency is a recently described form of hyperphenylalaninemia (HPA) [1]. HPA represents a metabolic condition caused by a deficiency in either phenylalanine (Phe) hydroxylase (PAH) or in one of the enzymes involved in the biosynthesis or regeneration of tetrahydrobiopterin (BH4) [2]. BH4 is the natural cofactor of PAH, tyrosine hydroxylase (TH), tryptophan hydroxylases (TPHs), and alkylglycerol monooxygenase, as well as all isoforms of nitric oxide synthase [3].

Type
Chapter
Information
Movement Disorders and Inherited Metabolic Disorders
Recognition, Understanding, Improving Outcomes
 , pp. 290 - 295
Publisher: Cambridge University Press
Print publication year: 2020

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References

Anikster, Y, Haack, TB, Vilboux, T, et al. Biallelic mutations in DNAJC12 cause hyperphenylalaninemia, dystonia, and intellectual disability. Am J Hum Genet. 2017;100(2):257–66.Google Scholar
Blau, N, Van Spronsen, FJ, Levy, HL. Phenylketonuria. Lancet. 2010;376:1417–27.CrossRefGoogle ScholarPubMed
Werner, ER, Blau, N, Thöny, B. Tetrahydrobiopterin: Biochemistry and pathophysiology. Biochem J. 2011;438:397–414.Google Scholar
Bouchereau, J, Huttlin, EL, Guarani, V, et al. DNAJC12: A molecular chaperone involved in proteostasis, PKU, biogenic amines metabolism and beyond? Mol Genet Metab. 2018;123(3):285–6.CrossRefGoogle ScholarPubMed
Blau, N, Martinez, A, Hoffmann, GF, Thony, B. DNAJC12 deficiency: A new strategy in the diagnosis of hyperphenylalaninemias. Mol Genet Metab. 2018;123:1–5.CrossRefGoogle ScholarPubMed
van Spronsen, FJ, Himmelreich, N, Rufenacht, V, et al. Heterogeneous clinical spectrum of DNAJC12-deficient hyperphenylalaninemia: From attention deficit to severe dystonia and intellectual disability. J Med Genet. 2017;doi:10.1136/jmedgenet-2017-104875.Google Scholar
Straniero, L, Guella, I, Cilia, R, et al. DNAJC12 and dopa-responsive non-progressive parkinsonism. Ann Neurol. 2017;82(4):640–6.Google Scholar
Leal, F, Navarrete, R, Castro, M, et al. Spanish hyperphenylalaninemia cases bearing a high frequent mutation in the DNAJC12 gene. J Inborn Error Metab Screen. 2017;5:131.Google Scholar
Feng, Y, Liu, S, Tang, C, et al. Identification of an inherited pathogenic DNAJC12 variant in a patient with hyperphenylalalinemia. Clin Chim Acta. 2018;doi:10.1016/j.cca.2018.09.002.Google Scholar
Veenma, D, Cordeiro, D, Sondheimer, N, Mercimek-Andrews, S. DNAJC12-associated developmental delay, movement disorder, and mild hyperphenylalaninemia identified by whole-exome sequencing re-analysis. Eur J Hum Genet. 2018;26(12):1867–70.CrossRefGoogle ScholarPubMed
de Sain-van der Velden, MGM, Kuper, WFE, Kuijper, MA, et al. Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12. JIMD Rep. 2018;42:99–103.Google Scholar
Kampinga, HH, Craig, EA. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol. 2010;11(8):579–92.Google ScholarPubMed
Dekker, SL, Kampinga, HH, Bergink, S. DNAJs: More than substrate delivery to HSPA. Front Mol Biosci. 2015;2:35.CrossRefGoogle ScholarPubMed
Cadieux-Dion, M, Andermann, E, Lachance-Touchette, P, et al. Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease. Clin Genet. 2013;83(6):571–5.CrossRefGoogle ScholarPubMed
Fontaine, SN, Zheng, D, Sabbagh, JJ, et al. DNAJ/HSC70 chaperone complexes control the extracellular release of neurodegenerative-associated proteins. EMBO J. 2016;35(14):1537–49.Google Scholar
Edvardson, S, Cinnamon, Y, Ta-Shma, A, et al. A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoating co-chaperone auxilin, is associated with juvenile parkinsonism. PLoS One. 2012;7(5):e36458.Google Scholar
Rajput, A, Ross, JP, Bernales, CQ, et al. VPS35 and DNAJC13 disease-causing variants in essential tremor. Eur J Hum Genet. 2015;23(6):887–8.Google Scholar
Gustavsson, EK, Trinh, J, Guella, I, et al. DNAJC13 genetic variants in parkinsonism. Mov Disord. 2015;30(2):273–8.Google Scholar
Ito, N, Kamiguchi, K, Nakanishi, K, et al. A novel nuclear DNAJ protein, DNAJC8, can suppress the formation of spinocerebellar ataxia 3 polyglutamine aggregation in a J-domain independent manner. Biochem Biophys Res Commun. 2016;474(4):626–33.CrossRefGoogle Scholar
Ojala, T, Polinati, P, Manninen, T, et al. New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies. Pediatr Res. 2012;72(4):432–7.CrossRefGoogle ScholarPubMed
Himmelreich, N, Hoffmann, GF, Blau, N. Expression pattern of phenylalanine hydroxylase variants is regulated by co-chaperone DNAJC12. Mol Genet Metab. 2018;123:210.Google Scholar
Jung-Kc, K, Himmelreich, N, Prestegard, K. S, et al. Phenylalanine hydroxylase variants interact with the co-chaperone DNAJC12. Hum Mutat. 2019;40:483–494.Google Scholar

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