Array CGH in molecular diagnosis of mental retardation—A study of 150 Finnish patients

Abstract

We report on the results of an array comparative genomic hybridization (array CGH) study of 150 karyotypically normal Finnish patients with idiopathic mental retardation and/or dysmorphic features and/or malformations. Using high-resolution microarray analysis, we sought to identify clinically relevant microdeletions and microduplications in these patients. The results were confirmed using other methods and compared with findings reported in recent publications and internet databases. Small aberrations of potential clinical significance were found in 28 (18.6%) of the 150 patients. Eight of the identified aberrations are known to cause syndromes, 4 affected the X chromosome in males, 4 were familial, and 13 have yet to be associated with a phenotype. This study demonstrates the benefits of array CGH in clinical diagnostics of developmental disorders. Further, our findings give evidence of new syndromes.

19p13.3 Aberrations Are Associated with Dysmorphic Features and Deviant Psychomotor Development

“…1 b). These aberrations overlap in an area of 651 kb, located at 39.27 to 45.78 Mb (probes A_16_ P41125007 to A_14_P108593), which covers 20 known genes ( table 1 ) [Siggberg et al, 2010]. QPCR analysis confirmed the array CGH results of both patients.…”

“…Data were extracted and analyzed, as described previously [Siggberg et al, 2010], using the Feature Extraction V.9.5.3.1 the CGH Analytics V.3.5.14 software. Annotations are based on human genome build 18.…”

“…We present 2 children with overlapping aberrations at 19p13.3 detected using array CGH [Siggberg et al, 2010]. Furthermore, we describe the exact location as well as the genetic content of these aberrations.…”

Evaluation of Real-Time Quantitative PCR as a Standard Cytogenetic Diagnostic Tool for Confirmation of Microarray (aCGH) Results and Determination of Inheritance

“…Various strategies have been described for follow-up analysis, including repeat aCGH testing, fluorescence in situ hybridization (FISH), microsatellite analysis, and multiplex ligationdependent probe amplification (MLPA) for specific genes (Sebat et al, 2007;Schluth et al, 2008;Siggberg et al, 2010).…”

Clinical utility of next-generation sequencing in neurodevelopmental disorders: non-syndromic intellectual disability as a model

“…It has been shown that approximately 15% of ID cases are caused by visible cytogenetic anomalies (aneuploidies, gross deletions, inversions and rearrangements), [25] and ~15-20% are due to submicroscopic aberrations and pathogenic copy number variants. [25][26][27][28][29][30][31][32] X-linked forms are estimated to account for only 5-10% of ID cases, [33] which means that the vast majority of the underlying genetic defects remain elusive and are likely to be autosomal. [22,25] In total, approximately 2,500 genes are estimated to be involved in monogenic causes of ID.…”