engleski

Chromosomal microarray in clinical diagnosis of cerebral palsy

Cerebral palsy (CP) is a group of non-progressive disorders of posture, tone, and/or movement. It is caused by a non-progressive lesion of the developing brain or brain malformation. Recent studies have implicated that genetic factors could contribute to diagnosis of CP or even cause CP. Potentially deleterious genomic copy number variants (CNVs) have been found in several CP cohorts, but estimates varied considerably depending on study criteria. The goal of this study is to define diagnostic utility of chromosomal microarray in children with CP, with well-defined phenotype according to Surveillance of cerebral palsy in Europe (SCPE) criteria. This study included 79 patients with CP, referred to the Department of Medical Genetics and Reproductive Health, Children’s Hospital Zagreb. All of them had confirmed CP diagnosis by the criteria of SCPE. The analysis was conducted using Agilent 60K oligonucleotide array-based comparative genomic hybridization. Clinically relevant variants were detected in 7 of 79 patients (8, 86%): deletions 14q32.31q32.33, 1q21.1q21.2, 15q11.2, 17p13.3 and 22q11.2 ; duplications 1q21.1q21.2 and Xq28 (in male patient). Variants of unknown significance (VOUS) were present in 5 patients (6, 33%): duplications 15q11.2, 3p26.3p26.2, 18p11.31 and Xq28 (in female patient) and deletion 17p12. Remaining patients had negative test results. Among the patients with clinically important variants, three had brain MRI classified as maldevelopment, three as predominant white matter injury, and one patient with 22q11.2 deletion as predominant grey matter injury. The genomic architecture of CP is highly complex, similar to other neurodevelopmental disorders. Continued analysis and reporting of CNV findings alongside massively parallel SNV analyses are needed to expand our knowledge of CP. Better understanding of all the possible genes involved in CP etiology is the cornerstone for understanding neurobiology of CP. This work was supported by Scientific Center of Excellence for Reproductive and Regenerative Medicine and by the EU through the European Regional Development Fund, under grant agreement No. KK.01.1.1.01.0008, project „Reproductive and Regenerative Medicine - Exploring New Platforms and Potentials”.

cerebral palsy, chromosomal microarray, copy number variants

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