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Pediatrik Nörolojide Klinik Fenotipler ve Kromozomal Mikrodelesyon/Duplikasyonlar Arasındaki İlişki

Year 2021, Volume: 23 Issue: 1, 97 - 109, 30.04.2021

Sevim Türay Recep Eröz Esra Habiloğlu Nadide Melike Sav

https://doi.org/10.18678/dtfd.881659
Cited By: 1

Abstract

Amaç: Bu çalışmanın amacı, günlük pediatrik nöroloji pratiğinde kromozomal mikrodizi analizinin (chromosomal microarray analysis, CMA) tanısal kullanışlılığını saptamak ve bu testi gerektiren hastalar için kılavuz olan klinik parametreler belirlemektir.
Gereç ve Yöntemler: Pediatrik nöroloji kliniğimize 2018 ve 2020 yılları arasında çeşitli nedenlerle başvuran global gelişme geriliği/zihinsel yetersizlik (global developmental delay/intellectual disability, GDD/ID) olan 91 hastanın CMA sonuçları incelendi. CMA’da del/dup tespit edilen 34 (%37,4) hastanın ve normal CMA’ya sahip olan 57 (%62,6) hastanın demografik ve klinik verileri karşılaştırıldı.
Bulgular: İki grup arasında yaş, cinsiyet, doğum şekli, doğum zamanı gibi demografik özellikler bakımından istatistiksel olarak anlamlı bir farklılık yoktu. Dismorfizm, hipotoni ve miyelinizasyon anormallikleri CMA’da del/dup olan hastalarda normal CMA’lı hastalara göre önemli ölçüde daha sıktı. Normal CMA grubunda makrosefali ve obezite sıklığı daha yüksekti ve bu grupta epileptik hastalardaki generalize konvulsiyon sıklığı daha yüksekti. Analizde del/dup saptanan 34 vakadan 19'u (%55,9) patojenik, 15'i (%44,1) klinik önemi bilinmeyen (muhtemelen patojenik, muhtemelen iyi huylu ve sınıflandırılamayan) olarak kabul edildi.
Sonuç: CMA pahalı, zahmetli ve zaman alan bir test olduğundan, CMA talep edilirken klinik parametrelerin dikkate alınması yüksek tanısal verimlilik sağlayacaktır. Dismorfizm, hipotoni ve miyelinizasyon gecikmesi olan GDD/ID hastalarında kopya sayısı değişiklikleri yüksek olasılıkla saptanabilir. Bu hastalarda farklı bir etyoloji düşündüren herhangi bir bulgunun olmadığı durumlarda, CMA pediatrik nöroloji pratiğinde tercih edilebilir bir genetik analizdir.

Keywords

Kromozomal mikrodizi analizi; pediatrik nöroloji; miyelinizasyon geriliği; hipotoni; global gelişme geriliği; zihinsel yetersizlik

References

  • Yeargin-Allsopp M, Murphy CC, Cordero JF, Decouflé P, Hollowell JG. Reported biomedical causes and associated medical conditions for mental retardation among 10-year-old children, metropolitan Atlanta, 1985 to 1987. Dev Med Child Neurol. 1997;39(3):142-9.
  • Petersen MC, Kube, DA, Palmer FB. Classification of developmental delays. Semin Pediatr Neurol. 1998;5(1):2-14.
  • Shevell M. Global developmental delay and mental retardation or intellectual disability: conceptualization, evaluation, and etiology. Pediatr Clin North. 2008;55(5):1071-84.
  • Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first- tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86(5): 749-64.
  • Battaglia A, Doccini V, Bernardini L, Novelli A, Loddo S, Capalbo A, et al. Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features. Eur J Paediatr Neurol. 2013;17(6):589-99.
  • Yalaz K, Epir S. The Denver Developmental Screening Test: normative data for Ankara children. Turk J Pediatr. 1983;25(4):245-58.
  • Roid GH. Stanford-Binet intelligence scales, 5th ed. Itasca, IL: Riverside Publishing; 2003.
  • Wechsler D. Wechsler Intelligence Scale for Children, 3rd ed. San Antonio, TX: The Psychological Corporation; 2006.
  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
  • Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51(4):676-85.
  • Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-77.
  • Jasper HH. The ten-twenty electrode system of the international federation. Electroencephalogr Clin Neurophysiol. 1958;10:371-75.
  • Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST, Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011;13(7):680-85.
  • Gürkan H, Atli EI, Atli E, Bozatli L, Altay MA, Yalçıntepe S, et al. Chromosomal microarray analysis in Turkish patients with unexplained developmental delay and intellectual developmental disorders. Noro Psikiyatr Ars. 2020;57(3):177-91.
  • Shoukier M, Klein N, Auber B, Wickert J, Schröder J, Zoll B, et al. Array CGH in patients with developmental delay or intellectual disability: are there phenotypic clues to pathogenic copy number variants? Clin Genet. 2013;83(1):53-65.
  • Tan AP, Mankad K, Gonçalves FG, Talenti G, Alexia E. Macrocephaly: Solving the diagnostic dilemma. Top Magn Reson Imaging. 2018;27(4):197-217.
  • Lu XY, Phung MT, Shaw CA, Pham K, Neil SE, Patel A, et al. Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics. 2008;122(6):1310-8.
  • Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, et al. A copy number variation morbidity map of developmental delay. Nat Genet. 2011;43(9):838-46.
  • Hu T, Zhang Z, Wang J, Li Q, Zhu H, Lai Y, et al. Chromosomal aberrations in pediatric patients with developmental delay/intellectual disability: A single-center clinical investigation. Biomed Res Int. 2019;2019:9352581.
  • Stalman SE, Solanky N, Ishida M, Alemán-Charlet C, Abu-Amero S, Alders M, et al. Genetic analyses in small-for-gestational-age newborns. J Clin Endocrinol Metab. 2018;103(3):917-25.
  • Micleaa D, Al-Khzouza C, Osan S, Bucerzan S, Cret V, Popp RA, et al. Genomic study via chromosomal microarray analysis in a group of Romanian patients with obesity and developmental disability/intellectual disability. J Pediatr Endocrinol Metab. 2019;32(7):667-74.
  • Vuillaume ML, Naudion S, Banneau G, Diene G, Cartault A, Cailley D, et al. New candidate loci identified by array-CGH in a cohort of 100 children presenting with syndromic obesity. Am J Med Genet A. 2014;164A(8):1965-75.
  • Harris SR. Congenital hypotonia: clinical and developmental assessment. Dev Med Child Neurol. 2008;50(12):889-92.
  • Olson H, Shen Y, Avallone J, Sheidley BR, Pinsky R, Bergin AM, et al. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014;75(6):943-58.
  • Mefford HC, Yendle SC, Hsu C, Cook J, Geraghty E, McMahon JM, et al. Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol. 2011;70(6):974-85.
  • Reinthaler EM, Lal D, Lebon S, Hildebrand MS, Dahl HH, Regan BM, et al. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy. Hum Mol Genet. 2014;23(22):6069-80.
  • Mullen SA, Carvill GL, Bellows S, Bayly MA, Trucks H, Lal D, et al. Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology. 2013;81(17):1507-14.
  • Addis L, Rosch RE, Valentin A, Makoff A, Robinson R, Everett KV, et al. Analysis of rare copy number variation in absence epilepsies. Neurol Genet. 2016;2(2):e56.
  • Hartmann C, von Spiczak S, Suls A, Weckhuysen S, Buyse G, Vilain C, et al. Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis. Epilepsia. 2015;56(3):e26-32.
  • Pérez-Palma E, Helbig I, Klein KM, Anttila V, Horn H, Reinthaler EM, et al. Heterogeneous contribution of microdeletions in the development of common generalised and focal epilepsies. J Med Genet. 2017;54(9):598-606.
  • Coppola A, Cellini E, Stamberger H, Saarentaus E, Cetica V, Lal D, et al. Diagnostic implications of genetic copy number variation in epilepsy plus. Epilepsia. 2019;60(4):689-706.
  • Peycheva V, Kamenarova K, Ivanova N, Stamatov D, Avdjieva-Tzavella D, Alexandrova I, et al. Chromosomal microarray analysis of Bulgarian patients with epilepsy and intellectual disability. Gene. 2018;667:45-55.
  • Mithyantha R, Kneen R, McCann E, Gladstone M. Current evidence-based recommendations on investigating children with global developmental delay. Arch Dis Child. 2017;102(11):1071-6.
  • Heide S, Keren B, Billette de Villemeur T, Chantot-Bastaraud S, Depienne C, Nava C, et al. Copy number variations found in patients with a corpus callosum abnormality and intellectual disability. J Pediatr. 2017;185:160-6.e1.
  • Romaniello R, Marelli S, Giorda R, Bedeschi MF, Bonaglia MC, Arrigoni F, et al. Clinical characterization, genetics, and long-term follow-up of a large cohort of patients with agenesis of the corpus callosum. J Child Neurol. 2017;32(1):60-71.
  • Ciaccio C, Pantaleoni C, Bulgheroni S, Sciacca F, D'Arrigo S. Chromosomal microarray analysis has a poor diagnostic yield in children with developmental delay/intellectual disability when concurrent cerebellar anomalies are present. Cerebellum. 2020;19(5):629-35.
  • Vigdorovich N, Ben-Sira L, Blumkin L, Precel R, Nezer I, Yosovich K, et al. Brain white matter abnormalities associated with copy number variants. Am J Med Genet A. 2020;182(1):93-103.
  • Michelson DJ, Shevell MI, Sherr EH, Moeschler JB, Gropman AL, Ashwal S. Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2011;77(17):1629-35.
  • D'Arrigo S, Gavazzi F, Alfei E, Zuffardi O, Montomoli C, Corso B, et al. The diagnostic yield of array comparative genomic hybridization is high regardless of severity of intellectual disability/developmental delay in children. J Child Neurol. 2016;31(6):691-9.

The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology

Year 2021, Volume: 23 Issue: 1, 97 - 109, 30.04.2021

Sevim Türay Recep Eröz Esra Habiloğlu Nadide Melike Sav

https://doi.org/10.18678/dtfd.881659
Cited By: 1

Abstract

Aim: The aim of this study was to determine the diagnostic utility of chromosomal microarray analysis (CMA) in daily pediatric neurology practice and to identify the guiding clinical parameters for patients requiring this test.
Material and Methods: The CMA results for 91 patients with global developmental delay/intellectual disability (GDD/ID) admitted to our pediatric neurology clinic for various reasons between 2018 and 2020 were examined. Demographical and clinical data for 34 patients (37.4%) in whom del/dup was determined at CMA and 57 patients (62.6%) with normal CMA were compared.
Results: There was no statistically significant difference between two groups in terms of demographic characteristics such as age, gender, type of delivery, gestational age, etc. Dysmorphisms, hypotonia, myelination abnormalities were significantly more frequent in patients with del/dup than in patients with normal result. The frequency of macrocephaly and obesity was higher in the normal group, and that of generalized seizures was higher among epileptic patients in this group. Nineteen (55.9%) of the 34 cases who have del/dup detected at analysis were regarded as pathogenic, 15 (44.1%) as uncertain clinical significance (likely pathogenic, likely benign and no subclassification).
Conclusion: Since CMA is an expensive, laborious, and time-consuming test, considering clinical parameters when requesting CMA will yield high diagnostic efficiency. A high possibility of copy number variants may be predicted in GDD/ID patients with dysmorphisms, hypotonia, and myelination delay. CMA should represent the genetic analysis of choice in pediatric neurology practice in case of no finding suggesting a different etiology in these patients.

Keywords

Chromosomal microarray analysis; pediatric neurology; myelination delay; hypotonia; global developmental delay; intellectual disability

References

  • Yeargin-Allsopp M, Murphy CC, Cordero JF, Decouflé P, Hollowell JG. Reported biomedical causes and associated medical conditions for mental retardation among 10-year-old children, metropolitan Atlanta, 1985 to 1987. Dev Med Child Neurol. 1997;39(3):142-9.
  • Petersen MC, Kube, DA, Palmer FB. Classification of developmental delays. Semin Pediatr Neurol. 1998;5(1):2-14.
  • Shevell M. Global developmental delay and mental retardation or intellectual disability: conceptualization, evaluation, and etiology. Pediatr Clin North. 2008;55(5):1071-84.
  • Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first- tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86(5): 749-64.
  • Battaglia A, Doccini V, Bernardini L, Novelli A, Loddo S, Capalbo A, et al. Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features. Eur J Paediatr Neurol. 2013;17(6):589-99.
  • Yalaz K, Epir S. The Denver Developmental Screening Test: normative data for Ankara children. Turk J Pediatr. 1983;25(4):245-58.
  • Roid GH. Stanford-Binet intelligence scales, 5th ed. Itasca, IL: Riverside Publishing; 2003.
  • Wechsler D. Wechsler Intelligence Scale for Children, 3rd ed. San Antonio, TX: The Psychological Corporation; 2006.
  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
  • Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51(4):676-85.
  • Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-77.
  • Jasper HH. The ten-twenty electrode system of the international federation. Electroencephalogr Clin Neurophysiol. 1958;10:371-75.
  • Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST, Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011;13(7):680-85.
  • Gürkan H, Atli EI, Atli E, Bozatli L, Altay MA, Yalçıntepe S, et al. Chromosomal microarray analysis in Turkish patients with unexplained developmental delay and intellectual developmental disorders. Noro Psikiyatr Ars. 2020;57(3):177-91.
  • Shoukier M, Klein N, Auber B, Wickert J, Schröder J, Zoll B, et al. Array CGH in patients with developmental delay or intellectual disability: are there phenotypic clues to pathogenic copy number variants? Clin Genet. 2013;83(1):53-65.
  • Tan AP, Mankad K, Gonçalves FG, Talenti G, Alexia E. Macrocephaly: Solving the diagnostic dilemma. Top Magn Reson Imaging. 2018;27(4):197-217.
  • Lu XY, Phung MT, Shaw CA, Pham K, Neil SE, Patel A, et al. Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics. 2008;122(6):1310-8.
  • Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, et al. A copy number variation morbidity map of developmental delay. Nat Genet. 2011;43(9):838-46.
  • Hu T, Zhang Z, Wang J, Li Q, Zhu H, Lai Y, et al. Chromosomal aberrations in pediatric patients with developmental delay/intellectual disability: A single-center clinical investigation. Biomed Res Int. 2019;2019:9352581.
  • Stalman SE, Solanky N, Ishida M, Alemán-Charlet C, Abu-Amero S, Alders M, et al. Genetic analyses in small-for-gestational-age newborns. J Clin Endocrinol Metab. 2018;103(3):917-25.
  • Micleaa D, Al-Khzouza C, Osan S, Bucerzan S, Cret V, Popp RA, et al. Genomic study via chromosomal microarray analysis in a group of Romanian patients with obesity and developmental disability/intellectual disability. J Pediatr Endocrinol Metab. 2019;32(7):667-74.
  • Vuillaume ML, Naudion S, Banneau G, Diene G, Cartault A, Cailley D, et al. New candidate loci identified by array-CGH in a cohort of 100 children presenting with syndromic obesity. Am J Med Genet A. 2014;164A(8):1965-75.
  • Harris SR. Congenital hypotonia: clinical and developmental assessment. Dev Med Child Neurol. 2008;50(12):889-92.
  • Olson H, Shen Y, Avallone J, Sheidley BR, Pinsky R, Bergin AM, et al. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014;75(6):943-58.
  • Mefford HC, Yendle SC, Hsu C, Cook J, Geraghty E, McMahon JM, et al. Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol. 2011;70(6):974-85.
  • Reinthaler EM, Lal D, Lebon S, Hildebrand MS, Dahl HH, Regan BM, et al. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy. Hum Mol Genet. 2014;23(22):6069-80.
  • Mullen SA, Carvill GL, Bellows S, Bayly MA, Trucks H, Lal D, et al. Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology. 2013;81(17):1507-14.
  • Addis L, Rosch RE, Valentin A, Makoff A, Robinson R, Everett KV, et al. Analysis of rare copy number variation in absence epilepsies. Neurol Genet. 2016;2(2):e56.
  • Hartmann C, von Spiczak S, Suls A, Weckhuysen S, Buyse G, Vilain C, et al. Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis. Epilepsia. 2015;56(3):e26-32.
  • Pérez-Palma E, Helbig I, Klein KM, Anttila V, Horn H, Reinthaler EM, et al. Heterogeneous contribution of microdeletions in the development of common generalised and focal epilepsies. J Med Genet. 2017;54(9):598-606.
  • Coppola A, Cellini E, Stamberger H, Saarentaus E, Cetica V, Lal D, et al. Diagnostic implications of genetic copy number variation in epilepsy plus. Epilepsia. 2019;60(4):689-706.
  • Peycheva V, Kamenarova K, Ivanova N, Stamatov D, Avdjieva-Tzavella D, Alexandrova I, et al. Chromosomal microarray analysis of Bulgarian patients with epilepsy and intellectual disability. Gene. 2018;667:45-55.
  • Mithyantha R, Kneen R, McCann E, Gladstone M. Current evidence-based recommendations on investigating children with global developmental delay. Arch Dis Child. 2017;102(11):1071-6.
  • Heide S, Keren B, Billette de Villemeur T, Chantot-Bastaraud S, Depienne C, Nava C, et al. Copy number variations found in patients with a corpus callosum abnormality and intellectual disability. J Pediatr. 2017;185:160-6.e1.
  • Romaniello R, Marelli S, Giorda R, Bedeschi MF, Bonaglia MC, Arrigoni F, et al. Clinical characterization, genetics, and long-term follow-up of a large cohort of patients with agenesis of the corpus callosum. J Child Neurol. 2017;32(1):60-71.
  • Ciaccio C, Pantaleoni C, Bulgheroni S, Sciacca F, D'Arrigo S. Chromosomal microarray analysis has a poor diagnostic yield in children with developmental delay/intellectual disability when concurrent cerebellar anomalies are present. Cerebellum. 2020;19(5):629-35.
  • Vigdorovich N, Ben-Sira L, Blumkin L, Precel R, Nezer I, Yosovich K, et al. Brain white matter abnormalities associated with copy number variants. Am J Med Genet A. 2020;182(1):93-103.
  • Michelson DJ, Shevell MI, Sherr EH, Moeschler JB, Gropman AL, Ashwal S. Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2011;77(17):1629-35.
  • D'Arrigo S, Gavazzi F, Alfei E, Zuffardi O, Montomoli C, Corso B, et al. The diagnostic yield of array comparative genomic hybridization is high regardless of severity of intellectual disability/developmental delay in children. J Child Neurol. 2016;31(6):691-9.
There are 39 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Sevim Türay 0000-0001-6002-052X

Recep Eröz 0000-0003-0840-2613

Esra Habiloğlu This is me 0000-0001-8234-3469

Nadide Melike Sav 0000-0003-1520-6426

Publication Date April 30, 2021
Submission Date February 17, 2021
Published in Issue Year 2021 Volume: 23 Issue: 1

Cite

APA Türay, S., Eröz, R., Habiloğlu, E., Sav, N. M. (2021). The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology. Duzce Medical Journal, 23(1), 97-109. https://doi.org/10.18678/dtfd.881659
AMA Türay S, Eröz R, Habiloğlu E, Sav NM. The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology. Duzce Med J. April 2021;23(1):97-109. doi:10.18678/dtfd.881659
Chicago Türay, Sevim, Recep Eröz, Esra Habiloğlu, and Nadide Melike Sav. “The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology”. Duzce Medical Journal 23, no. 1 (April 2021): 97-109. https://doi.org/10.18678/dtfd.881659.
EndNote Türay S, Eröz R, Habiloğlu E, Sav NM (April 1, 2021) The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology. Duzce Medical Journal 23 1 97–109.
IEEE S. Türay, R. Eröz, E. Habiloğlu, and N. M. Sav, “The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology”, Duzce Med J, vol. 23, no. 1, pp. 97–109, 2021, doi: 10.18678/dtfd.881659.
ISNAD Türay, Sevim et al. “The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology”. Duzce Medical Journal 23/1 (April 2021), 97-109. https://doi.org/10.18678/dtfd.881659.
JAMA Türay S, Eröz R, Habiloğlu E, Sav NM. The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology. Duzce Med J. 2021;23:97–109.
MLA Türay, Sevim et al. “The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology”. Duzce Medical Journal, vol. 23, no. 1, 2021, pp. 97-109, doi:10.18678/dtfd.881659.
Vancouver Türay S, Eröz R, Habiloğlu E, Sav NM. The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology. Duzce Med J. 2021;23(1):97-109.

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