Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Background: Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. Methods: We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children’s Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. Results: We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. Conclusions: This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability.
Abstract
Background: Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. Methods: We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children’s Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. Results: We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. Conclusions: This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability.
참고문헌 (39)
- Shevell M, "Practice parameter: evaluation of the child 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, 60, pp.367~380 (2003)[DOI]
- Riggs ER, "Chromosomal microarray impacts clinical management", Clin Genet, 85, pp.147~153 (2014)[DOI]
- Tao VQ, "The clinical impact of chromosomal microarray on paediatric care in Hong Kong", PLoS One, 9, pp.e109629~ (2014)[DOI]
- Miller DT, "Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies", Am J Hum Genet, 86, pp.749~764 (2010)[DOI]
- Kearney HM, "American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants", Genet Med, 13, pp.680~685 (2011)[DOI]
- Trakadis Y, "Microarray as a first genetic test in global developmental delay: a cost-effectiveness analysis", Dev Med Child Neurol, 53, pp.994~999 (2011)[DOI]
- 신새암, "Routine Chromosomal Microarray Analysis is Necessary in Korean Patients With Unexplained Developmental Delay", Mental Retardation, Annals of Laboratory Medicine, pp.2015, 35(5)[DOI]
- Sharma P, "Application of chromosomal microarrays in the evaluation of intellectual disability", global developmental delay patients-A study from a tertiary care genetic centre in India, 2016, pp.590, 109~119
- 이차곤, "Array-Based Comparative Genomic Hybridization in 190 Korean Patients with Developmental Delay and", or Intellectual Disability: A Single Tertiary Care University Center Study, 2013, pp.54(6), 1463~1470[DOI]
- 변정혜, "Application of Array-Based Comparative Genomic Hybridization to Pediatric Neurologic Diseases", Yonsei Medical Journal, 55(1), pp.30~36 (2014), 연세대학교의과대학
- ISCN, "An international system for human cytogenetic nomenclature" (2013), S. Karger
- ISCN, "An international system for human cytogenetic nomenclature" (2016), S. Karger
- Di Gregorio E, "Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH", Mol Cytogenet, 7, pp.82~ (2014)[DOI]
- Siggberg L, "Array CGH in molecular diagnosis of mental retardation-a study of 150 Finnish patients", Am J Med Genet A, 152a, pp.1398~1410 (2010)
- Chong WW, "Performance of chromosomal microarray for patients with intellectual disabilities", developmental delay, autism, and multiple congenital anomalies in a Chinese cohort, 2014, pp.7, 34~
- Xiang B, "Genome-wide oligonucleotide array comparative genomic hybridization for etiological diagnosis of mental retardation: a multicenter experience of 1,499 clinical cases", J Mol Diagn, 12, pp.204~212 (2010)[DOI]
- Fan YS, "Detection of pathogenic gene copy number variations in patients with mental retardation by genomewide oligonucleotide array comparative genomic hybridization", Hum Mutat, 28, pp.1124~1132 (2007)[DOI]
- Battaglia A, "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, 17, pp.589~599 (2013)[DOI]
- Pickering DL, "Array-based comparative genomic hybridization analysis of 1,176 consecutive clinical genetics investigations", Genet Med, 10, pp.262~266 (2008)[DOI]
- D'Arrigo S, "The diagnostic yield of array comparative genomic hybridization is high regardless of severity of intellectual disability", developmental delay in children, 2016, pp.31, 691~699
- Shoukier M, "Array CGH in patients with developmental delay or intellectual disability: are there phenotypic clues to pathogenic copy number variants?", Clin Genet, 83, pp.53~65 (2013)[DOI]
- Shimada S, "Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications", Brain Dev, 37, pp.515~526 (2015)[DOI]
- Battaglia A, "GeneReviews" (2008), University of Washington
- Battaglia A, "GeneReviews" (2002), University of Washington
- Bertini V, "Isolated 6q terminal deletions: an emerging new syndrome", Am J Med Genet A, 140, pp.74~81 (2006)
- Lin S, "Chromosome 10q26 deletion syndrome: two new cases and a review of the literature", Mol Med Rep, 14, pp.5134~5140 (2016)[DOI]
- Smith ACM, "GeneReviews" (2001), University of Washington
- Maya I, "Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome", Am J Med Genet A, 164a, pp.1940~1946 (2014)
- McDonald-McGinn DM, "GeneReviews" (1999), University of Washington
- Bohm LA, "Neuroradiographic findings in 22q11.2 deletion syndrome", Am J Med Genet A, 173, pp.2158~2165 (2017)[DOI]
- Briggs TA, "The value of microarray-based comparative genomic hybridisation (aCGH) testing in the paediatric clinic", Arch Dis Child, 100, pp.728~731 (2015)[DOI]
- Rosello M, "Phenotype profiling of patients with intellectual disability and copy number variations", Eur J Paediatr Neurol, 18, pp.558~566 (2014)[DOI]
- Buizer-Voskamp JE, "Increased paternal age and the influence on burden of genomic copy number variation in the general population", Hum Genet, 132, pp.443~450 (2013)[DOI]
- Nowakowska BA, "Parental insertional balanced translocations are an important cause of apparently de novo CNVs in patients with developmental anomalies", Eur J Hum Genet, 20, pp.166~170 (2012)[DOI]
- Sanders SR, "Interstitial deletion of chromosome 2p16.2p21", Clin Dysmorphol, 12, pp.183~185 (2003)
- Eto K, "Microdeletions of 3p21.31 characterized by developmental delay, distinctive features, elevated serum creatine kinase levels, and white matter involvement", Am J Med Genet A, 161A, pp.3049~3056 (2013)
- Haldeman-Englert CR, "A 3.1-Mb microdeletion of 3p21.31 associated with cortical blindness, cleft lip, CNS abnormalities, and developmental delay", Eur J Med Genet, 52, pp.265~268 (2009)[DOI]
- Tassano E, "Phenotypic and genetic characterization of a patient with a de novo interstitial 14q24.1q24.3 deletion", Mol Cytogenet, 7, pp.49~ (2014)[DOI]
- Ji J, "DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies", Eur J Hum Genet, 23, pp.1473~1481 (2015)[DOI]