Homozygous mutation in the eukaryotic translation initiation factor 2alpha phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature and intellectual disability

Human Molecular Genetics

Volumn 24, Issue 22, 2015, Pages 6293-6300

  Kernohan, Kristin D ^a   Tétreault, Martine ^c   Liwak Muir, Urszula ^a   Geraghty, Michael T ^a,b   Qin, Wen ^a   Venkateswaran, Sunita ^b   Davila, Jorge ^a   Holcik, Martin ^a   Majewski, Jacek ^c   Richer, Julie ^a   Boycott, Kym M ^a   Boycott, Kym ^b   MacKenzie, Alex ^b   Brudno, Michael ^d   Bulman, Dennis ^b   Dyment, David ^b   Care4Rare Canada Consortium, ^a  

^a CHILDREN S HOSPITAL OF EASTERN ONTARIO   (Canada)

^b UNIVERSITY OF OTTAWA   (Canada)

^c MCGILL UNIVERSITY   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

INITIATION FACTOR 2ALPHA; PHOSPHOPROTEIN PHOSPHATASE 1; PPP1C PROTEIN; PROTEIN PHOSPHATASE 1 REGULATORY SUBUNIT 15B; THYROTROPIN; UNCLASSIFIED DRUG; CELL CYCLE PROTEIN; INITIATION FACTOR 2; PROTEIN SUBUNIT;

ALCOHOL CONSUMPTION; ANTHROPOMETRIC PARAMETERS; ARTICLE; BINDING SITE; BRAIN DISEASE; CASE REPORT; CELL STRESS; CHILD; CLINICAL ASSESSMENT; CONSANGUINITY; CORD DELAYED MYELINATION; DEMYELINATING DISEASE; DISEASE ASSOCIATION; DISEASE SEVERITY; ENZYME ACTIVATION; EXOME; FACIES; FEMALE; GENE IDENTIFICATION; GENE MUTATION; GENE SEQUENCE; GENETIC ASSOCIATION; GESTATIONAL AGE; GROWTH DISORDER; GROWTH RETARDATION; HEAD CIRCUMFERENCE; HOMOZYGOSITY; HUMAN; HYPOPLASTIC BRAINSTEM; HYPOTHYROIDISM; INTELLECTUAL IMPAIRMENT; INTRAUTERINE GROWTH RETARDATION; MALE; MATERNAL SMOKING; MEDICAL HISTORY; MICROCEPHALY; MISSENSE MUTATION; MOTOR PERFORMANCE; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN FUNCTION; PROTEIN INTERACTION; SHORT STATURE; SIBLING; TRANSLATION INITIATION; BODY HEIGHT; DNA SEQUENCE; DWARFISM; ENZYMOLOGY; GENETICS; HOMOZYGOTE; METABOLISM; MUTATION; PHOSPHORYLATION; PRESCHOOL CHILD; PROTEIN SUBUNIT; PROTEIN SYNTHESIS;

BINDING SITES; BODY HEIGHT; CELL CYCLE PROTEINS; CHILD, PRESCHOOL; CONSANGUINITY; DWARFISM; EUKARYOTIC INITIATION FACTOR-2; FEMALE; HOMOZYGOTE; HUMANS; INTELLECTUAL DISABILITY; MALE; MICROCEPHALY; MUTATION; MUTATION, MISSENSE; PHOSPHORYLATION; PROTEIN BIOSYNTHESIS; PROTEIN PHOSPHATASE 1; PROTEIN SUBUNITS; SEQUENCE ANALYSIS, DNA;

EID: 84949009457     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv337     Document Type: Article

References (32)

1. Hinnebusch, A.G. and Lorsch, J.R. (2012) The mechanism of eukaryotic translation initiation: New insights and challenges. Cold Spring Harb. Persp. Biol., 4, 1-21.
2. Kapp, L.D. and Lorsch, J.R. (2004) The molecular mechanics of eukaryotic translation. Ann. Rev. Biochem., 73, 657-704.
3. Novoa, I., Zeng, H., Harding, H.P. and Ron, D. (2001) Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J. Cell Biol., 153, 101-1022.
4. Jousse, C., Oyadomari, S., Novoa, I., Lu, P., Zhang, Y., Harding, H.P. and Ron, D. (2003) Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CREP, promotes survival of stressed cells. J. Cell Biol., 163, 767-775.
5. Connor, J.H.,Weiser, D.C., Li, S., Hallenbeck, J.M. and Shenolikar, S. (2001) Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Mol. Cell. Biol., 21, 6841-6850.
6. Kojima, E., Takeuchi, A., Haneda, M., Yagi, A., Hasegawa, T., Yamaki, K., Takeda, K., Akira, S., Shimokata, K. and Isobe, K. (2003) The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress: elucidation by GADD34-deficient mice. FASEB J., 17, 1573-1575.
7. Scheper, G.C., Vanderknaap, M.S. and Proud, C.G. (2007) Translation matters: protein synthesis defects in inherited disease. Nat. Rev. Genet., 8, 711-723.
8. Fogli, A., Dionisi-Vici, C., Deodato, F., Bartuli, A., Boespflug-Tanguy, O. and Bertini, E. (2002) A severe variant of childhood ataxia with central hypomyelination/vanishing white matter leukoencephalopathy related to EIF21B5 mutation. Neurology, 59, 1966-1968.
9. vanderknaap, M.S., Leegwater, P.A., Konst, A.A., Visser, A., Naidu, S., Oudejans, C.B., Schutgens, R.B. and Pronk, J.C. (2002) Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Ann. Neurol., 51, 264-270.
10. Draptchinskaia, N., Gustavsson, P., Andersson, B., Pettersson, M., Willig, T.N., Dianzani, I., Ball, S., Tchernia, G., Klar, J., Matsson, H. et al. (1999) The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat. Genet., 21, 169-175.
11. Gazda, H.T., Kho, A.T., Sanoudou, D., Zaucha, J.M., Kohane, I.S., Sieff, C.A. and Beggs, A.H. (2006) Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia. Stem Cells, 24, 2034-2044.
12. Menne, T.F., Goyenechea, B., Sanchez-Puig, N., Wong, C.C., Tonkin, L.M., Ancliff, P.J., Brost, R.L., Costanzo, M., Boone, C. and Warren, A.J. (2007) The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat. Genet., 39, 486-495.
13. Thiel, C.T., Horn, D., Zabel, B., Ekici, A.B., Salinas, K., Gebhart, E., Ruschendorf, F., Sticht, H., Spranger, J., Muller, D. et al. (2005) Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am. J. Hum. Genet., 77, 795-806.
14. Antonellis, A., Ellsworth, R.E., Sambuughin, N., Puls, I., Abel, A., Lee-Lin, S.Q., Jordanova, A., Kremensky, I., Christodoulou, K., Middleton, L.T. et al. (2003) Glycyl tRNA synthetase mutations in charcot-marie-tooth disease type 2D and distal spinal muscular atrophy type V. Am. J. Hum. Genet., 72, 1293-1299.
15. James, P.A., Cader, M.Z., Muntoni, F., Childs, A.M., Crow, Y.J. and Talbot, K. (2006) Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene. Neurology, 67, 1710-1712.
16. Jordanova, A., Irobi, J., Thomas, F.P., Vandijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., Devriendt, E., Guergueltcheva, V. et al. (2006) Disrupted function and axonal distribution of mutant tyrosyl-TRNA synthetase in dominant intermediate charcot-marie-tooth neuropathy. Nat. Genet., 38, 197-202.
17. Mclaughlin, H.M., Sakaguchi, R., Liu, C., Igarashi, T., Pehlivan, D., Chu, K., Iyer, R., Cruz, P., Cherukuri, P.F., Hansen, N.F. et al. (2010) Compound heterozygosity for loss-of-function lysyltRNA synthetase mutations in a patient with peripheral neuropathy. Am. J. Hum. Genet., 87, 560-566.
18. Chakraborty, P.K., Schmitz-Abe, K., Kennedy, E.K., Mamady, H., Naas, T., Durie, D., Campagna, D.R., Lau, A., Sendamarai, A.K., Wiseman, D.H. et al. (2014) Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood, 124, 2867-2871.
19. Kumar, P., Henikoff, S. and Ng, P.C. (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat. Protoc., 4, 1073-1081.
20. Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., Kondrashov, A.S. and Sunyaev, S.R. (2010) A method and server for predicting damaging missense mutations. Nat. Methods, 7, 248-249.
21. Harding, H.P., Zhang, Y., Scheuner, D., Chen, J.J., Kaufman, R.J. and Ron, D. (2009) Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha (eIF2alpha) dephosphorylation in mammalian development. Proc. Natl Acad. Sci. USA, 106, 1832-1837.
22. Zeng, N., Li, Y., He, L., Xu, X., Galicia, V., Deng, C. and Stiles, B.L. (2011) Adaptive basal phosphorylation of eIF2alpha is responsible for resistance to cellular stress-induced cell death in Pten-null hepatocytes. Mol. Cancer Res., 9, 1708-1717.
23. Marciniak, S.J., Yun, C.Y., Oyadomari, S., Novoa, I., Zhang, Y., Jungreis, R., Nagata, K., Harding, H.P. and Ron, D. (2004) CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Gene. Dev., 18, 3066-3077.
24. Kloft, N., Neukirch, C., Vonhoven, G., Bobkiewicz ,W.,Weis, S., Boller, K. and Husmann, M. (2012) A subunit of eukaryotic translation initiation factor 2alpha-phosphatase (CREP/PPP1R15B) regulates membrane traffic. J. Biol. Chem., 287, 35299-35317.
25. Fogli, A., Schiffmann, R., Hugendubler, L., Combes, P., Bertini, E., Rodriguez, D., Kimball, S.R. and Boespflug-Tanguy, O. (2004) Decreased guanine nucleotide exchange factor activity in eIF2B-mutated patients. Eur. J. Hum. Genet., 12, 561-566.
26. Vankollenburg, B., Thomas, A.A., Vermeulen, G., Bertrand, G.A., vanberkel, C.G., Pronk, J.C., Proud, C.G., Vanderknaap, M.S. and Scheper, G.C. (2006) Regulation of protein synthesis in lymphoblasts from vanishing white matter patients. Neurobiol. Dis., 21, 496-504.
27. Senee, V., Vattem, K.M., Delepine, M., Rainbow, L.A., Haton, C., Lecoq, A., Shaw, N.J., Robert, J.J., Rooman, R., Diatloff-Zito, C. et al. (2004)Wolcott-rallison syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. Diabetes, 53, 1876-1883.
28. Zhang, P., Mcgrath, B., Li, S., Frank, A., Zambito, F., Reinert, J., Gannon, M., Ma, K., Mcnaughton, K. and Cavener, D.R. (2002) The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol. Cell Biol., 22, 3864-3874.
29. Srour, M., Schwartzentruber, J., Hamdan, F.F., Ospina, L.H., Patry, L., Labuda, D., Massicotte, C., Dobrzeniecka, S., Capo-Chichi, J.M., Papillon-Cavanagh, S. et al. (2012) Mutations in C5ORF42 cause Joubert syndrome in the French canadian population. Am. J. Hum. Genet., 90, 693-700.
30. Li, H. and Durbin, R. (2009) Fast and accurate short read alignment with Burrows-wheeler transform. Bioinformatics, 25, 1754-1760.
31. Mckenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M. et al. (2010) The genome analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res., 20, 1297-1303.
32. Wang, K., Li, M. and Hakonarson, H. (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucl. Acids. Res., 38, e164.