Saadet Andrews

portrait of saadet andrews

Professor

8-42B Medical Sciences Building
Office: 780-407-2533
Email: saadet@ualberta.ca

Dr. Andrews completed medical school and pediatric residency in Türkiye. She trained in pediatrics and clinical metabolic genetics at the Department of Pediatrics, Vienna General Hospital, University of Vienna, Austria. She completed biochemical genetics fellowship training accredited by Canadian College of Medical Geneticist at the University of British Columbia in Vancouver. She finished one-year pediatric neurology fellowship in the Division of Neurology, Department of Pediatrics, University of British Columbia. She completed her PhD in “Creatine deficiency syndrome: contributions to selective and newborn screening and treatment” at the Free University, Amsterdam, The Netherlands. She worked as metabolic staff physician at British Columbia Children’s Hospital and neurometabolic staff physician at The Hospital for Sick Children. She developed the first inherited neurotransmitter disease and epilepsy genetics clinics at The Hospital for Sick Children.

Neonatal encephalopathy occurs in 1–7 infants per 1,000 live-term births and results either in death or in permanent neurological damage. The Andrews’ laboratory studies gene discovery for neonatal encephalopathy using whole genome sequencing to identify underlying genetic defects in essential energy metabolism and neurotransmitter pathways in newborns with neonatal encephalopathy and neonatal brain injury. These discoveries will allow development of model organisms to provide novel insights into the pathogenesis of neonatal encephalopathy. These insights will pave the ground towards the development of targeted neuroprotective treatment strategies to likely improve the health outcomes in neonatal encephalopathy.

Epilepsy is a common neurological disorder and its prevalence is 3-6/1000 in childhood. In approximately 30% of affected children, their epilepsy is refractory to medical management. Dr. Andrews’ laboratory will study gene discovery for epilepsy using whole genome sequencing with a specific interest in the area of refractory epilepsy responsive to the ketogenic diet. Identification of novel genes will help understanding the underlying mechanisms how the ketogenic diet stops seizures. These discoveries will allow the development of model organisms to provide novel insights into the pathogenesis of refractory epilepsy. These studies will also allow us to predict response to the ketogenic diet, decide duration of the ketogenic diet as well as investigate for alternative therapies to treat seizures based on the gene function in the biochemical pathways.

ALDH7A1 deficiency is one of the neurometabolic epilepsies. The current treatments do not prevent neurodevelopmental disability even if started in infancy and applied strictly. Dr. Andrews developed first knock-out zebrafish model to study ALDH7A1 deficiency neuropathogenesis and to use this model for small molecule high throughput drug screening.

Selected publications

1. Tolchin D, Yeager JP, Prasad P, Dorrani N, Russi AS, Martinez-Agosto JA, Haseeb A, Angelozzi M, Santen GWE, Ruivenkamp C, Mercimek-Andrews S, Depienne C, Kuechler A, Mikat B, Ludecke HJ, Bilan F, Le Guyader G, Gilbert-Dussardier B, Keren B, Heide S, Haye D, Van Esch H, Keldermans L, Ortiz D, Lancaster E, Krantz ID, Krock BL, Pechter KB, Arkader A, Medne L, DeChene ET, Calpena E, Melistaccio G, Wilkie AOM, Suri M, Foulds N; Genomics England Research Consortium, Begtrup A, Henderson LB, Forster C, Reed P, McDonald MT, McConkie-Rosell A, Thevenon J, Le Tanno P, Coutton C, Tsai ACH, Stewart S, Maver A, Gorazd R, Pichon O, Nizon M, Cogné B, Isidor B, Martin-Coignard D, Stoeva R, Lefebvre V, Le Caignec C. De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas. Am J Hum Genet. 2020 May 19:S0002-9297(20)30124-5.

2. Pearson TS, Gilbert L, Opladen T, Garcia-Cazorla A, Mastrangelo M, Leuzzi V, Tay SKH, Sykut-Cegielska J, Pons R, Mercimek-Andrews S, Kato M, Lücke T, Oppebøen M, Kurian MA, Steel D, Manti F, Meeks KD, Jeltsch K, Flint L. AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients. J Inherit Metab Dis. 2020 May 5. doi: 10.1002/jimd.12247.

3. Johnson BV, Kumar R, Oishi S, Alexander S, Kasherman M, Vega MS, Ivancevic A, Gardner A, Domingo D, Corbett M, Parnell E, Yoon S, Oh T, Lines M, Lefroy H, Kini U, Van Allen M, Grønborg S, Mercier S, Küry S, Bézieau S, Pasquier L, Raynaud M, Afenjar A, Billette de Villemeur T, Keren B, Désir J, Van Maldergem L, Marangoni M, Dikow N, Koolen DA, VanHasselt PM, Weiss M, Zwijnenburg P, Sa J, Reis CF, López-Otín C, Santiago-Fernández O, Fernández-Jaén A, Rauch A, Steindl K, Joset P, Goldstein A, Madan-Khetarpal S, Infante E, Zackai E, Mcdougall C, Narayanan V, Ramsey K, Mercimek-Andrews S, Pena L, Shashi V; Undiagnosed Diseases Network, Schoch K, Sullivan JA, Pinto E Vairo F, Pichurin PN, Ewing SA, Barnett SS, Klee EW, Perry MS, Koenig MK, Keegan CE, Schuette JL, Asher S, Perilla-Young Y, Smith LD, Rosenfeld JA, Bhoj E, Kaplan P, Li D, Oegema R, van Binsbergen E, van der Zwaag B, Smeland MF, Cutcutache I, Page M, Armstrong M, Lin AE, Steeves MA, Hollander ND, Hoffer MJV, Reijnders MRF, Demirdas S, Koboldt DC, Bartholomew D, Mosher TM, Hickey SE, Shieh C, Sanchez-Lara PA, Graham JM Jr, Tezcan K, Schaefer GB, Danylchuk NR, Asamoah A, Jackson KE, Yachelevich N, Au M, Pérez-Jurado LA, Kleefstra T, Penzes P, Wood SA, Burne T, Pierson TM, Piper M, Gécz J, Jolly LA. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling. Biol Psychiatry. 2020 Jan 15;87(2):100-112

4. Moravej H, Altassan R, Jaeken J, Enns GM, Ellaway C, Balasubramaniam S, De Lonlay P, Coman D, Mercimek-Andrews S, Witters P, Morava E. Hypoglycemia in CDG patients due to PMM2 mutations: Follow up on hyperinsulinemic patients. JIMD Rep. 2019: 25;51(1):76-81.

5. Guo H, Bettella E, Marcogliese PC, Zhao R, Andrews JC, Nowakowski TJ, Gillentine MA, Hoekzema K, Wang T, Wu H, Jangam S, Liu C, Ni H, Willemsen MH, van Bon BW, Rinne T, Stevens SJC, Kleefstra T, Brunner HG, Yntema HG, Long M, Zhao W, Hu Z, Colson C, Richard N, Schwartz CE, Romano C, Castiglia L, Bottitta M, Dhar SU, Erwin DJ, Emrick L, Keren B, Afenjar A, Zhu B, Bai B, Stankiewicz P, Herman K; University of Washington Center for Mendelian Genomics, Mercimek-Andrews S, Juusola J, Wilfert AB, Abou Jamra R, Büttner B, Mefford HC, Muir AM, Scheffer IE, Regan BM, Malone S, Gecz J, Cobben J, Weiss MM, Waisfisz Q, Bijlsma EK, Hoffer MJV, Ruivenkamp CAL, Sartori S, Xia F, Rosenfeld JA, Bernier RA, Wangler MF, Yamamoto S, Xia K, Stegmann APA, Bellen HJ, Murgia A, Eichler EE. Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders. Nat Commun. 2019;10(1):4679.

6. Jilani A*, Matviychuk D, Blaser S, Dyack S, Mathieu J, Asuri N. Prasad, Prasad C, Kyriakopoulou L, Mercimek-Andrews S. High diagnostic yield of direct Sanger sequencing in the diagnosis of neuronal ceroid lipofuscinoses. JIMD Reports 2019; 2019 Sep 3;50(1):20-30.

7. Costain G, Cordeiro D, Matviychuk D, Mercimek-Andrews S. Clinical Application of Targeted Next-Generation Sequencing Panels and Whole Exome Sequencing in Childhood Epilepsy. Neuroscience. 2019 2019 Oct 15;418:291-310.

8. O'Donnell-Luria AH, Pais LS, Faundes V, Wood JC, Sveden A, Luria V, Abou Jamra R, Accogli A, Amburgey K, Anderlid BM, Azzarello-Burri S, Basinger AA, Bianchini C, Bird LM, Buchert R, Carre W, Ceulemans S, Charles P, Cox H, Culliton L, Currò A; Deciphering Developmental Disorders (DDD) Study, Demurger F, Dowling JJ, Duban-Bedu B, Dubourg C, Eiset SE, Escobar LF, Ferrarini A, Haack TB, Hashim M, Heide S, Helbig KL, Helbig I, Heredia R, Héron D, Isidor B, Jonasson AR, Joset P, Keren B, Kok F, Kroes HY, Lavillaureix A, Lu X, Maas SM, Maegawa GHB, Marcelis CLM, Mark PR, Masruha MR, McLaughlin HM, McWalter K, Melchinger EU, Mercimek-Andrews S, Nava C, Pendziwiat M, Person R, Ramelli GP, Ramos LLP, Rauch A, Reavey C, Renieri A, Rieß A, Sanchez-Valle A, Sattar S, Saunders C, Schwarz N, Smol T, Srour M, Steindl K, Syrbe S, Taylor JC, Telegrafi A, Thiffault I, Trauner DA, van der Linden H Jr, van Koningsbruggen S, Villard L, Vogel I, Vogt J, Weber YG, Wentzensen IM, Widjaja E, Zak J, Baxter S, Banka S, Rodan LH. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy. Am J Hum Genet. 2019;104(6):1210-1222.

9. Sega AG, Mis EK, Lindstrom K, Mercimek-Andrews S, Ji W, Cho MT, Juusola J, Konstantino M, Jeffries L, Khokha MK, Lakhani SA. De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy. J Med Genet. 2019 Feb;56(2):113-122.

10. Cordeiro D*, Bullivant G*, Siriwardena K, Evans A, Kobayashi J, Cohn RD, Mercimek-Andrews S. Genetic landscape of pediatric movement disorders and management implications. Neurol Genet. 2018 Sep 26;4(5):e265.

11. Cordeiro D, Bullivant G*, Cohn RD, Raiman J, Mercimek-Andrews S. Outcome of Patients With Inherited Neurotransmitter Disorders. Can J Neurol Sci. 2018 Sep;45(5):571-576.

12. Reijnders MRF, Miller KA, Alvi M, Goos JAC, Lees MM, de Burca A, Henderson A, Kraus A, Mikat B, de Vries BBA, Isidor B, Kerr B, Marcelis C, Schluth-Bolard C, Deshpande C, Ruivenkamp CAL, Wieczorek D; Deciphering Developmental Disorders Study, Baralle D, Blair EM, Engels H, Lüdecke HJ, Eason J, Santen GWE, Clayton-Smith J, Chandler K, Tatton-Brown K, Payne K, Helbig K, Radtke K, Nugent KM, Cremer K, Strom TM, Bird LM, Sinnema M, Bitner-Glindzicz M, van Dooren MF, Alders M, Koopmans M, Brick L, Kozenko M, Harline ML, Klaassens M, Steinraths M, Cooper NS, Edery P, Yap P, Terhal PA, van der Spek PJ, Lakeman P, Taylor RL, Littlejohn RO, Pfundt R, Mercimek-Andrews S, Stegmann APA, Kant SG, McLean S, Joss S, Swagemakers SMA, Douzgou S, Wall SA, Küry S, Calpena E, Koelling N, McGowan SJ, Twigg SRF, Mathijssen IMJ, Nellaker C, Brunner HG, Wilkie AOM. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder. Am J Hum Genet. 2018;102(6):1195-1203.

13. Khaikin Y*, Sidky S*, Abdenur J, Anastasi A, Ballhausen D, Buoni S, Chan A, Cheillan D, Dorison N, Goldenberg A, Goldstein J, Hofstede FC, Jacquemont ML, Koeberl DD, Lion-Francois L, Lund AM, Mention K, Mundy H, O'Rourke D, Pitelet G, Raspall-Chaure M, Tassini M, Billette de Villemeur T, Williams M, Salomons GS, Mercimek-Andrews S. Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. Eur J Paediatr Neurol. 2018;22(3):369-379.

14. Bruun TUJ*, Sidky S*, Bandeira AO, Debray FG, Ficicioglu C, Goldstein J, Joost K, Koeberl DD, Luísa D, Nassogne MC, O'Sullivan S, Õunap K, Schulze A, van Maldergem L, Salomons GS, Mercimek-Andrews S. Treatment outcome of creatine transporter deficiency: international retrospective cohort study. Metab Brain Dis. 2018;33(3):875-884.

15. Hewson S, Mercimek-Andrews S. Prevalence of genetic diagnoses and glucose transporter 1 deficiency in patients with drug resistant epilepsy on the ketogenic diet. Can J Neurol Sci. 2018;45(1):93-96.

16. Hamdan FF, Myers CT, Cossette P, Lemay P, Spiegelman D, Laporte AD, Nassif C, Diallo O, Monlong J, Cadieux-Dion M, Dobrzeniecka S, Meloche C, Retterer K, Cho MT, Rosenfeld JA, Bi W, Massicotte C, Miguet M, Brunga L, Regan BM, Mo K, Tam C, Schneider A, Hollingsworth G; Deciphering Developmental Disorders Study, FitzPatrick DR, Donaldson A, Canham N, Blair E, Kerr B, Fry AE, Thomas RH, Shelagh J, Hurst JA, Brittain H, Blyth M, Lebel RR, Gerkes EH, Davis-Keppen L, Stein Q, Chung WK, Dorison SJ, Benke PJ, Fassi E, Corsten-Janssen N, Kamsteeg EJ, Mau-Them FT, Bruel AL, Verloes A, Õunap K, Wojcik MH, Albert DVF, Venkateswaran S, Ware T, Jones D, Liu YC, Mohammad SS, Bizargity P, Bacino CA, Leuzzi V, Martinelli S, Dallapiccola B, Tartaglia M, Blumkin L, Wierenga KJ, Purcarin G, O'Byrne JJ, Stockler S, Lehman A, Keren B, Nougues MC, Mignot C, Auvin S, Nava C, Hiatt SM, Bebin M, Shao Y, Scaglia F, Lalani SR, Frye RE, Jarjour IT, Jacques S, Boucher RM, Riou E, Srour M, Carmant L, Lortie A, Major P, Diadori P, Dubeau F, D'Anjou G, Bourque G, Berkovic SF, Sadleir LG, Campeau PM, Kibar Z, Lafrenière RG, Girard SL, Mercimek-Mahmutoglu S, Boelman C, Rouleau GA, Scheffer IE, Mefford HC, Andrade DM, Rossignol E, Minassian BA, Michaud JL. High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. Am J Hum Genet. 2017;101(5):664-685.

17. Zabinyakov N*, Bullivant G*, Cao F, Fernandez Ojeda M, Jia ZP, Wen XY, Dowling JJ, Salomons GS, Mercimek-Andrews S. Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology. PLoS One. 2017 Oct 20;12(10):e0186645. doi: 10.1371/journal.pone.0186645. eCollection 2017.

18. Bruun TUJ*, DesRoches CL, Wilson D, Chau V, Nakagawa T, Yamasaki M, Hasegawa S, Fukao T, Marshall C, Mercimek-Andrews S. Prospective cohort study for identification of underlying genetic causes in neonatal encephalopathy using whole-exome sequencing. Genet Med. 2018;20(5):486-494.

19. Al Teneiji A*, Bruun TU*, Sidky S, Cordeiro D, Cohn RD, Mendoza-Londono R, Moharir M, Raiman J, Siriwardena K, Kyriakopoulou L, Mercimek-Mahmutoglu S. Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II. Mol Genet Metab. 2017;120(3):235-242.

20. DesRoches CL*, Bruun T*, Wang P, Marshall CR, Mercimek-Mahmutoglu S. Arginine-Glycine Amidinotransferase Deficiency and Functional Characterization of Missense Variants in GATM. Hum Mutat. 2016;37(9):926-32.

21. Desroches CL*, Patel J*, Wang P, Minassian B, Marshall CR, Salomons GS, Mercimek-Mahmutoglu S. Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene. Molecular Genetics and Genomics. 2015;290:2163-71.

22. Mercimek-Mahmutoglu S, Sidky S*, Hyland K, Patel J*, Donner E, Logan W, Mendoza-Londono R, Mahendranath M, Raiman J, Schulze A, Siriwardena K, Yoon G, Kyriakopolou L. Prevalence of inherited neurotransmitter disorders in patients with movement disorders and epilepsy: a retrospective cohort study. Orphanet J Rare Dis. 2015 Feb 8;10:12

23. Mercimek-Mahmutoglu S, Patel J*, Cordeiro D, Hewson S, Callen D, Donner EJ, Hahn CD, Kannu P, Kobayashi J, Minassian B, Moharir M, Siriwardena K, Weiss SK, Weksberg R, Snead OC. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia. 2015;56:707-16.

Please click the following links to view Dr. Saadet Andrews' publications: 
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