A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability of ATP8A2-related disorders caused by missense changes

Alsahli S, Alrifai MT, Tala A, Mutairi S, F. A., Alfadhel M (2018) Further delineation of the clinical phenotype of cerebellar Ataxia, Mental Retardation, and disequilibrium syndrome type 4. J Cent Nerv Syst Dis 10:1179573518759682. https://doi.org/10.1177/1179573518759682

Article  PubMed  PubMed Central  Google Scholar 

Coleman JA, Molday RS (2011) Critical role of the beta-subunit CDC50A in the stable expression, assembly, subcellular localization, and lipid transport activity of the P4-ATPase ATP8A2. J Biol Chem 286(19):17205–17216. https://doi.org/10.1074/jbc.M111.229419

Article  PubMed  PubMed Central  Google Scholar 

Tadini-Buoninsegni F, Mikkelsen SA, Mogensen LS, Molday RS, Andersen JP (2019) Phosphatidylserine flipping by the P4-ATPase ATP8A2 is electrogenic. Proc Natl Acad Sci U S A 116(33):16332–16337. https://doi.org/10.1073/pnas.1910211116

Article  PubMed  PubMed Central  Google Scholar 

Vestergaard AL, Coleman JA, Lemmin T, Mikkelsen SA, Molday LL, Vilsen B, Molday RS, Peraro D, M., Andersen JP (2014) Critical roles of isoleucine-364 and adjacent residues in a hydrophobic gate control of phospholipid transport by the mammalian P4-ATPase ATP8A2. Proc Natl Acad Sci U S A 111(14):E1334–1343. https://doi.org/10.1073/pnas.1321165111

Article  PubMed  PubMed Central  Google Scholar 

Lorent JH, Levental KR, Ganesan L, Rivera-Longsworth G, Sezgin E, Doktorova M, Lyman E, Levental I (2020) Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape. Nat Chem Biol 16(6):644–652. https://doi.org/10.1038/s41589-020-0529-6

Article  PubMed  PubMed Central  Google Scholar 

Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148(7):2207–2216

Article  PubMed  Google Scholar 

Martin SJ, Finucane DM, Amarante-Mendes GP, O’Brien GA, Green DR (1996) Phosphatidylserine externalization during CD95-induced apoptosis of cells and cytoplasts requires ICE/CED-3 protease activity. J Biol Chem 271(46):28753–28756. https://doi.org/10.1074/jbc.271.46.28753

Article  PubMed  Google Scholar 

Bevers EM, Comfurius P, van Rijn JL, Hemker HC, Zwaal RF (1982) Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 122(2):429–436. https://doi.org/10.1111/j.1432-1033.1982.tb05898.x

Article  PubMed  Google Scholar 

van den Eijnde SM, van den Hoff MJ, Reutelingsperger CP, van Heerde WL, Henfling ME, Vermeij-Keers C, Schutte B, Borgers M, Ramaekers FC (2001) Transient expression of phosphatidylserine at cell-cell contact areas is required for myotube formation. J Cell Sci 114(Pt 20):3631–3642. https://doi.org/10.1242/jcs.114.20.3631

Article  PubMed  Google Scholar 

Onat OE, Gulsuner S, Bilguvar K, Nazli Basak A, Topaloglu H, Tan M, Tan U, Gunel M, Ozcelik T (2013) Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion. Eur J Hum Genet 21(3):281–285. https://doi.org/10.1038/ejhg.2012.170

Article  PubMed  Google Scholar 

Cacciagli P, Haddad MR, Mignon-Ravix C, El-Waly B, Moncla A, Missirian C, Chabrol B, Villard L (2010) Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo balanced translocation and a severe neurological phenotype. Eur J Hum Genet 18(12):1360–1363. https://doi.org/10.1038/ejhg.2010.126

Article  PubMed  PubMed Central  Google Scholar 

Martín-Hernández E, Rodríguez-García ME, Camacho A, Matilla-Dueñas A, García-Silva MT, Quijada-Fraile P, Corral-Juan M, Tejada-Palacios P, de Las Heras RS, Arenas J, Martín MA, Martínez-Azorín F (2016) New ATP8A2 gene mutations associated with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. Neurogenetics 17(4):259–263. https://doi.org/10.1007/s10048-016-0496-y

Article  PubMed  Google Scholar 

Damásio J, Santos D, Morais S, Brás J, Guerreiro R, Sardoeira A, Cavaco S, Carrilho I, Barbot C, Barros J, Sequeiros J (2021) Congenital ataxia due to novel variant in ATP8A2. Clin Genet 100(1):79–83. https://doi.org/10.1111/cge.13954

Article  PubMed  Google Scholar 

McMillan HJ, Telegrafi A, Singleton A, Cho MT, Lelli D, Lynn FC, Griffin J, Asamoah A, Rinne T, Erasmus CE, Koolen DA, Haaxma CA, Keren B, Doummar D, Mignot C, Thompson I, Velsher L, Dehghani M, Mehrjardi V, Yoon MY, G (2018) Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy. Orphanet J Rare Dis 13(1):86. https://doi.org/10.1186/s13023-018-0825-3

Article  PubMed  PubMed Central  Google Scholar 

Zhu X, Libby RT, de Vries WN, Smith RS, Wright DL, Bronson RT, Seburn KL, John SW (2012) Mutations in a P-type ATPase gene cause axonal degeneration. PLoS Genet 8(8):e1002853. https://doi.org/10.1371/journal.pgen.1002853

Article  PubMed  PubMed Central  Google Scholar 

Luse SA, Chenard C, Finke EH (1967) The wabbler-lethal mouse. An electron microscopic study of the nervous system. Arch Neurol 17(2):153–161. https://doi.org/10.1001/archneur.1967.00470260043004

Article  PubMed  Google Scholar 

Xu Q, Yang GY, Liu N, Xu P, Chen YL, Zhou Z, Luo ZG, Ding X (2012) P4-ATPase ATP8A2 acts in synergy with CDC50A to enhance neurite outgrowth. FEBS Lett 586(13):1803–1812. https://doi.org/10.1016/j.febslet.2012.05.018

Article  PubMed  Google Scholar 

Coleman JA, Zhu X, Djajadi HR, Molday LL, Smith RS, Libby RT, John SW, Molday RS (2014) Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival. J Cell Sci 127(Pt 5):1138–1149. https://doi.org/10.1242/jcs.145052

Article  PubMed  PubMed Central  Google Scholar 

Carroll EW, Curtis RL, Sullivan DA, Melvin JL (1992) Wallerian degeneration in the optic nerve of the wabbler-lethal (wl/wl) mouse. Brain Res Bull 29(3–4):411–418. https://doi.org/10.1016/0361-9230(92)90077-b

Article  PubMed  Google Scholar 

Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9(4):357–359. https://doi.org/10.1038/nmeth.1923

Article  PubMed  PubMed Central  Google Scholar 

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R (2009) The sequence Alignment/Map format and SAMtools. Bioinformatics 25(16):2078–2079. https://doi.org/10.1093/bioinformatics/btp352

Article  PubMed  PubMed Central  Google Scholar 

Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, Levy-Moonshine A, Jordan T, Shakir K, Roazen D, Thibault J, Banks E, Garimella KV, Altshuler D, Gabriel S, DePristo MA (2013) From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinf 43(1110). https://doi.org/10.1002/0471250953.bi1110s43

Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38(16):e164. https://doi.org/10.1093/nar/gkq603

Article  PubMed  PubMed Central  Google Scholar 

Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, Collins RL, Laricchia KM, Ganna A, Birnbaum DP, Gauthier LD, Brand H, Solomonson M, Watts NA, Rhodes D, Singer-Berk M, England EM, Seaby EG, Kosmicki JA, MacArthur DG (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581(7809):434–443. https://doi.org/10.1038/s41586-020-2308-7

Article  PubMed  PubMed Central  Google Scholar 

Scott EM, Halees A, Itan Y, Spencer EG, He Y, Azab MA, Gabriel SB, Belkadi A, Boisson B, Abel L, Clark AG, Alkuraya FS, Casanova JL, Gleeson JG (2016) Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery. Nat Genet 48(9):1071–1076. https://doi.org/10.1038/ng.3592

Article  PubMed  PubMed Central  Google Scholar 

Ng PC, Henikoff S (2003) SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 31(13):3812–3814. https://doi.org/10.1093/nar/gkg509

Article  PubMed  PubMed Central  Google Scholar 

Adzhubei I, Jordan DM, Sunyaev SR (2013) Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. Chap. 7, Unit7.20 https://doi.org/10.1002/0471142905.hg0720s76

Article  PubMed  PubMed Central  Google Scholar 

Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M (2019) CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 47(D1):D886–d894. https://doi.org/10.1093/nar/gky1016

Article  PubMed  Google Scholar 

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