Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability
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초록
Purpose: The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplaineddevelopmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We alsoaimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). Materials and Methods: We collected clinical and CMA data from patients at Konyang University Hospital between September2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. Results: All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy,and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) wereconsidered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than inthose with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by83.3% (15/18) of the patients with pathogenic CMA. Conclusion: Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequentlyfound if patients have two or more clinical features in addition to DD/ID.
Abstract
Purpose: The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplaineddevelopmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We alsoaimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). Materials and Methods: We collected clinical and CMA data from patients at Konyang University Hospital between September2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. Results: All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy,and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) wereconsidered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than inthose with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by83.3% (15/18) of the patients with pathogenic CMA. Conclusion: Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequentlyfound if patients have two or more clinical features in addition to DD/ID.
참고문헌 (19)
- Leonard H, "The epidemiology of mental retardation: challenges and opportunities in the new millennium", Ment Retard Dev Disabil Res Rev, 8, pp.117~134 (2002)[DOI]
- Vissers LE, "Genetic studies in intellectual disability and related disorders", Nat Rev Genet, 17, pp.9~18 (2016)
- Rauch A, "Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation", Am J Med Genet A, 140, pp.2063~2074 (2006)
- 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]
- 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]
- Zilina O, "Chromosomal microarray analysis as a first-tier clinical diagnostic test: Estonian experience", Mol Genet Genomic Med, 2, pp.166~175 (2014)[DOI]
- 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~
- Howell KB, "High resolution chromosomal microarray in undiagnosed neurological disorders", J Paediatr Child Health, 49, pp.716~724 (2013)[DOI]
- 변정혜, "Application of Array-Based Comparative Genomic Hybridization to Pediatric Neurologic Diseases", Yonsei Medical Journal, 55(1), pp.30~36 (2014), 연세대학교의과대학
- Iourov IY, "Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies", Mol Cytogenet, 5, pp.46~ (2012)[DOI]
- Uwineza A, "Array-CGH analysis in Rwandan patients presenting development delay", intellectual disability with multiple congenital anomalies, 2014, pp.15, 79~
- Coulter ME, "Chromosomal microarray testing influences medical management", Genet Med, 13, pp.770~776 (2011)[DOI]
- Palmer E, "Changing interpretation of chromosomal microarray over time in a community cohort with intellectual disability", Am J Med Genet A, 164A, pp.377~385 (2014)
- Kim HJ, "A Korean family with KBG syndrome identified by ANKRD11 mutation, and phenotypic comparison of ANKRD11 mutation and 16q24.3 microdeletion", Eur J Med Genet, 58, pp.86~94 (2015)[DOI]
- Gilissen C, "Genome sequencing identifies major causes of severe intellectual disability", Nature, 511, pp.344~347 (2014)[DOI]
- Girirajan S, "Relative burden of large CNVs on a range of neurodevelopmental phenotypes", PLoS Genet, 7, pp.e1002334~ (2011)[DOI]
- Cooper GM, "A copy number variation morbidity map of developmental delay", Nat Genet, 43, pp.838~846 (2011)[DOI]
- Girirajan S, "Phenotypic heterogeneity of genomic disorders and rare copy-number variants", N Engl J Med, 367, pp.1321~1331 (2012)[DOI]
- 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]