RESUMO
BACKGROUND: The most prevalent type of structural variation in the human genome is represented by copy number variations that can affect transcription levels, sequence, structure and function of genes. METHOD: In the present study, we used the multiplex ligation-dependent probe amplification (MLPA) technique and quantitative PCR for the detection of copy number variation in 132 intellectually disabled male patients with normal karyotypes and negative fragile-X-testing. RESULTS: Ten of these patients (7.6%) showed copy number variation in the subtelomeric regions, including deletions and duplications. DISCUSSION: Duplications of the SECTM1 gene, located at 17q25.3, and of the FLJ22115 gene, located at 20p13, could be associated with phenotype alterations. This study highlights the relevance in the aetiology of intellectual disability of subtelomeric rearrangements that can be screened by MLPA and other molecular techniques.
Assuntos
Dosagem de Genes/genética , Rearranjo Gênico/genética , Deficiência Intelectual/genética , Telômero/genética , Adolescente , Criança , Predisposição Genética para Doença/epidemiologia , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Reação em Cadeia da Polimerase , PrevalênciaRESUMO
Ring chromosomes are often associated with abnormal phenotypes due to loss of genomic material and also because of ring instability at mitosis after sister chromatid exchange events. We investigated ring chromosome instability in six patients with ring chromosomes 4, 14, 15, and 18 by examining 48- and 72-h lymphocyte cultures at the first, second and subsequent cell divisions after bromodeoxyuridine incorporation. Although most cells from all patients showed only one monocentric ring chromosome, ring chromosome loss and secondary aberrations were observed both in 48- and 72-h lymphocyte cultures and in metaphase cells of the different cell generations. We found no clear-cut correlation between ring size and ring instability; we also did not find differences between apparently complete rings and rings with genetic material loss. The cytogenetic findings revealed secondary aberrations in all ring chromosome patients. We concluded that cells with ring chromosome instability can multiply and survive in vivo, and that they can influence the patient's phenotype.