CGH microarray studies in idiopathic developmental/ cognitive impairment: association of historical and clinical features and the De Vries Score
Keywords:
Copy number variation, Developmental delay, Dysmorphism, Birth defects, PrenatalAbstract
Objective. Studies have confirmed that copy number variations(CNV) in the human genome contribute to the etiology of mentalretardation/ development delay/ congenital anomalies. We soughtto evaluate the use of a microarray in the context of a clinical geneticspractice, to determine if there were any specific clinical findingsthat predict the discovery of a CNV. Patients and methods. 334 caseswith idiopathic mental retardation/impairment/development delay/disability or a combination of these findings were studied using arraycomparative genomic hybridization (Signature Chip Version 4). Thesubjects had previously had a non diagnostic medical genetics evaluation.Clinical findings were collated by a chart review. Each patientwas scored according to a previously published clinical checklist by deVries and colleagues. Results. Of 334 patients, 8 were excluded due toa syndromic diagnosis being established by clinical and/or microarraytesting. Out of the remaining 326 patients, 33 (10%) showed CNVs,of which 5 were maternally inherited, 4 paternally inherited, 11 werede novo, and the origin of 13 remained unknown. The mean de Vriesscore was greater in the CNV group than in the non CNV group (4.17and 3.95, respectively). No patient in the CNV group had a score ofless than 3, while in the non CNV group, 12% of patients had scoresless than 3. Conclusions. The De Vries clinical score was higher inCNV cases compared to those with no CNV (p=0.04) but this differenceis unlikely to be clinically meaningful. Several features reachedstatistical significance of p<0.05 but we were unable to delineate patternsof features that might increase the yield of positive CNV results.Downloads
References
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Publishing, Inc.; 2000.
Curry CJ, Stevenson RE, Aughton D, Byrne J, Carey JC, Cassidy S, et al. Evaluation of mental retardation: recommendations of a Consensus Conference: American College of Medical Genetics. Am J Med Genet. 1997;72(4):468-77.
Hunter AG. Outcome of the routine assessment of patients with mental retardation in a genetics clinic. Am J Med Genet. 2000;90(1):60-8.
Opitz JM, Kaveggia EG, Durkin-Stamm MV and Pendleton E. Diagnostic/genetic studies in severe mental retardation. Birth Defects Orig Artic Ser. 1978;14(6B):1-38.
Shao L, Shaw CA, Lu XY, Sahoo T, Bacino CA, Lalani SR, et al. Identification of chromosome abnormalities in subtelomeric regions by microarray analysis: a study of 5,380 cases. Am J Med Genet A. 2008;146A(17):2242-51.
de Vries BB, White SM, Knight SJ, Regan R, Homfray T, Young ID, et al. Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. J Med Genet. 2001;38(3):145-50.
South ST, Rope AF, Lamb AN, Aston E, Glaus N, Whitby H, et al. Expansion in size of a terminal deletion: a paradigm shift for parental follow-up studies. J Med Genet. 2008;45(6):391-5.
Merritt JL and Lindor NM. Further clinical description of duplication of Williams-Beuren region presenting with congenital glaucoma and brachycephaly. Am J Med Genet A. 2008;146A(8):1055-8.
Shevell MI, Bejjani BA, Srour M, Rorem EA, Hall N and Shaffer LG. Array comparative genomic hybridization in global developmental delay. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(7):1101-8.
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(10):629-36.
Sagoo GS, Butterworth AS, Sanderson S, Shaw- Smith C, Higgins JP and Burton H. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med. 2009;11(3):139-46.
Bernardini L, Alesi V, Loddo S, Novelli A, Bottillo I, Battaglia A, et al. High-resolution SNP arrays in mental retardation diagnostics: how much do we gain? Eur J Hum Genet. 2010;18(2):178-85.
