Yonsei Med J.  2014 Jan;55(1):30-36. 10.3349/ymj.2014.55.1.30.

Application of Array-Based Comparative Genomic Hybridization to Pediatric Neurologic Diseases

Affiliations
  • 1Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. bleun@korea.ac.kr
  • 2Neodine Medical Institute, Seoul, Korea.

Abstract

PURPOSE
Array comparative genomic hybridization (array-CGH) is a technique used to analyze quantitative increase or decrease of chromosomes by competitive DNA hybridization of patients and controls. This study aimed to evaluate the benefits and yield of array-CGH in comparison with conventional karyotyping in pediatric neurology patients.
MATERIALS AND METHODS
We included 87 patients from the pediatric neurology clinic with at least one of the following features: developmental delay, mental retardation, dysmorphic face, or epilepsy. DNA extracted from patients and controls was hybridized on the Roche NimbleGen 135K oligonucleotide array and compared with G-band karyotyping. The results were analyzed with findings reported in recent publications and internet databases.
RESULTS
Chromosome imbalances, including 9 cases detected also by G-band karyotyping, were found in 28 patients (32.2%), and at least 19 of them seemed to be causally related to the abnormal phenotypes. Regarding each clinical symptom, 26.2% of 42 developmental delay patients, 44.4% of 18 mental retardation patients, 42.9% of 28 dysmorphic face patients, and 34.6% of 26 epilepsy patients showed abnormal array results.
CONCLUSION
Although there were relatively small number of tests in patients with pediatric neurologic disease, this study demonstrated that array-CGH is a very useful tool for clinical diagnosis of unknown genome abnormalities performed in pediatric neurology clinics.

Keyword

Comparative genomic hybridization; nervous system disease; child

MeSH Terms

Adolescent
Adult
Child
Child, Preschool
Comparative Genomic Hybridization/*methods
Female
Humans
Infant
Infant, Newborn
Karyotyping
Male
Nervous System Diseases/*genetics
Young Adult

Cited by  2 articles

Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability
Hyo Jeong Kim, Chang Il Park, Jae Woo Lim, Gyung Min Lee, Eunhae Cho, Hyon J. Kim
Yonsei Med J. 2018;59(3):431-437.    doi: 10.3349/ymj.2018.59.3.431.

Kleefstra syndrome combined with vesicoureteral reflux and rectourethral fistula: a case report and literature review
Chae Won Lee, Min Ji Park, Eun Joo Lee, Sangyoon Lee, Jinyoung Park, Jun Nyung Lee, So Mi Lee, Shin Young Jeong, Min Hyun Cho
Child Kidney Dis. 2022;26(2):111-115.    doi: 10.3339/ckd.22.039.


Reference

1. Slater HR, Bailey DK, Ren H, Cao M, Bell K, Nasioulas S, et al. High-resolution identification of chromosomal abnormalities using oligonucleotide arrays containing 116,204 SNPs. Am J Hum Genet. 2005; 77:709–726.
Article
2. Allanson JE, Cunniff C, Hoyme HE, McGaughran J, Muenke M, Neri G. Elements of morphology: standard terminology for the head and face. Am J Med Genet A. 2009; 149A:6–28.
Article
3. Hall BD, Graham JM Jr, Cassidy SB, Opitz JM. Elements of morphology: standard terminology for the periorbital region. Am J Med Genet A. 2009; 149A:29–39.
Article
4. de Kovel CG, Trucks H, Helbig I, Mefford HC, Baker C, Leu C, et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain. 2010; 133(Pt 1):23–32.
Article
5. Koolen DA, Reardon W, Rosser EM, Lacombe D, Hurst JA, Law CJ, et al. Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation. Eur J Hum Genet. 2005; 13:1019–1024.
Article
6. Phelan MC. Deletion 22q13.3 syndrome. Orphanet J Rare Dis. 2008; 3:14.
Article
7. Kleefstra T, van Zelst-Stams WA, Nillesen WM, Cormier-Daire V, Houge G, Foulds N, et al. Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype. J Med Genet. 2009; 46:598–606.
Article
8. Malmgren H, Sahlén S, Wide K, Lundvall M, Blennow E. Distal 3p deletion syndrome: detailed molecular cytogenetic and clinical characterization of three small distal deletions and review. Am J Med Genet A. 2007; 143A:2143–2149.
Article
9. Lenzini E, Ballarati L, Drigo P, Carrozzi M, Gambel-Benussi D, Giardino D, et al. 1q44-qter trisomy: clinical report and review of the literature. Genet Test Mol Biomarkers. 2009; 13:79–86.
10. Wisniewski L, Hassold T, Heffelfinger J, Higgins JV. Cytogenetic and clinical studies in five cases of inv dup(15). Hum Genet. 1979; 50:259–270.
Article
11. Scharer G, Brocker C, Vasiliou V, Creadon-Swindell G, Gallagher RC, Spector E, et al. The genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to mutations in ALDH7A1. J Inherit Metab Dis. 2010; 33:571–581.
Article
12. Yan J, Zhang F, Brundage E, Scheuerle A, Lanpher B, Erickson RP, et al. Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange. J Med Genet. 2009; 46:626–634.
Article
13. Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, et al. CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet. 2005; 14:1935–1946.
Article
14. Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med. 2008; 359:1685–1699.
Article
15. Sahoo T, Theisen A, Rosenfeld JA, Lamb AN, Ravnan JB, Schultz RA, et al. Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems. Genet Med. 2011; 13:868–880.
Article
16. Shinawi M, Liu P, Kang SH, Shen J, Belmont JW, Scott DA, et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2010; 47:332–341.
Article
17. Abou Jamra R, Wohlfart S, Zweier M, Uebe S, Priebe L, Ekici A, et al. Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity. Eur J Hum Genet. 2011; 19:1161–1166.
Article
18. Ropers HH. Genetics of intellectual disability. Curr Opin Genet Dev. 2008; 18:241–250.
Article
19. Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C, et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A. 2006; 140:2063–2074.
Article
20. Ravnan JB, Tepperberg JH, Papenhausen P, Lamb AN, Hedrick J, Eash D, et al. Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities. J Med Genet. 2006; 43:478–489.
Article
21. Knight SJ, Regan R, Nicod A, Horsley SW, Kearney L, Homfray T, et al. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet. 1999; 354:1676–1681.
Article
22. Ballif BC, Sulpizio SG, Lloyd RM, Minier SL, Theisen A, Bejjani BA, et al. The clinical utility of enhanced subtelomeric coverage in array CGH. Am J Med Genet A. 2007; 143A:1850–1857.
Article
23. Stankiewicz P, Beaudet AL. Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. Curr Opin Genet Dev. 2007; 17:182–192.
Article
24. Hochstenbach R, Buizer-Voskamp JE, Vorstman JA, Ophoff RA. Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research. Cytogenet Genome Res. 2011; 135:174–202.
Article
25. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, et al. Global variation in copy number in the human genome. Nature. 2006; 444:444–454.
Article
26. Xiang B, Zhu H, Shen Y, Miller DT, Lu K, Hu X, et al. Genome-wide oligonucleotide array comparative genomic hybridization for etiological diagnosis of mental retardation: a multicenter experience of 1499 clinical cases. J Mol Diagn. 2010; 12:204–212.
Article
27. Wagenstaller J, Spranger S, Lorenz-Depiereux B, Kazmierczak B, Nathrath M, Wahl D, et al. Copy-number variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation. Am J Hum Genet. 2007; 81:768–779.
Article
28. Hoyer J, Dreweke A, Becker C, Göhring I, Thiel CT, Peippo MM, et al. Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays. J Med Genet. 2007; 44:629–636.
Article
29. Friedman JM, Baross A, Delaney AD, Ally A, Arbour L, Armstrong L, et al. Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation. Am J Hum Genet. 2006; 79:500–513.
Article
30. Fan YS, Jayakar P, Zhu H, Barbouth D, Sacharow S, Morales A, et al. Detection of pathogenic gene copy number variations in patients with mental retardation by genomewide oligonucleotide array comparative genomic hybridization. Hum Mutat. 2007; 28:1124–1132.
Article
31. Mosca-Boidron AL, Bouquillon S, Faivre L, Callier P, Andrieux J, Marle N, et al. What can we learn from old microdeletion syndromes using array-CGH screening? Clin Genet. 2012; 82:41–47.
Article
32. Morimoto M, Usuku T, Tanaka M, Otabe O, Nishimura A, Ochi M, et al. Ring chromosome 14 with localization-related epilepsy: three cases. Epilepsia. 2003; 44:1245–1249.
Article
33. van Karnebeek CD, Quik S, Sluijter S, Hulsbeek MM, Hoovers JM, Hennekam RC. Further delineation of the chromosome 14q terminal deletion syndrome. Am J Med Genet. 2002; 110:65–72.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr