engleski

Diagnostic strategy integrating clinical, cytogenetic, FISH and molecular studies in evaluation of patients with developmental delay

We present the results of cytogenetic and molecular studies in 170 children referred to the Department of Medical Genetics for developmental and somatic delay, congenital malformation, dysmorphic features and behavioural problems of unknown etiology (common aneuploidy syndromes were excluded). The aim of this study was to determine the frequency of structural aberrations and to evaluate diagnostic algorithm that starts with clinical examination, followed by cytogenetic, FISH and molecular analysis. Cytogenetic analysis was carried out on slides obtained by peripheral blood culture using high resolution GTG-, RBG- and CBG-banding methods. FISH studies were performed using WCP-, CEP-, LSI-probes and subtelomere FISH screening assay. For understanding of the mechanism of formation, precise identification of breakpoints, and parental origin of rearrangements, additional FISH and molecular studies including both parents and sibs were performed. Cytogenetic analysis revealed structural chromosome aberrations in 12 (7.1%) out of 170 children. FISH analysis with microdeletion probes were performed in 127 out of 158 patients and microdeletions were identified in 14 (11.0%) cases. Rearrangements involving subtelomeric regions were detected in 2 (6.5%) out of 31 screened children. In our sample we identified 28 (16.5%) children with structural aberrations including 23 (13.5%) children with unbalanced rerrangements /dup(16) ; dup(8) ; der(15)t(15 ; 18) ; der(8)t(7 ; 8) ; der (X)t(X ; 6) ; del(2) ; del(14) ; r(9) ; psu idic(X) and 14interstitioal microdeletions/, 3 (1.8%) with apparently balanced aberrations /inv(13) ; t(6 ; 17) ; t(6 ; 19)/ and 2 (1.2%) with complex apparently balanced abnormalities /t(1 ; 4), t(2 ; 14), inv(3) ; t(6 ; 19), t(2 ; 13)/. This study demonstrates the usefulness of diagnostic strategy that integrates clinical, cytogenetic, FISH and molecular analysis in the identification of genome imbalances in patients with developmental delay.

Developmental delay; Cytogenetics; FISH; Molecular analysis

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