A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy.

Autor: Orlando V; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Di Tommaso S; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Alesi V; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Loddo S; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Genovese S; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Catino G; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Martucci L; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Roberti MC; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Trivisano M; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Dentici ML; Medical Genetics Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy.; Genetics and Rare Disease Research Division, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Specchio N; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Dallapiccola B; Genetics and Rare Disease Research Division, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Ferretti A; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy., Novelli A; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Oct 26; Vol. 23 (21). Date of Electronic Publication: 2022 Oct 26.
DOI: 10.3390/ijms232112900
Abstrakt: Complex genomic rearrangements (CGRs) are structural variants arising from two or more chromosomal breaks, which are challenging to characterize by conventional or molecular cytogenetic analysis (karyotype and FISH). The integrated approach of standard and genomic techniques, including optical genome mapping (OGM) and genome sequencing, is crucial for disclosing and characterizing cryptic chromosomal rearrangements at high resolutions. We report on a patient with a complex developmental and epileptic encephalopathy in which karyotype analysis showed a de novo balanced translocation involving the long arms of chromosomes 2 and 18. Microarray analysis detected a 194 Kb microdeletion at 2q24.3 involving the SCN2A gene, which was considered the likely translocation breakpoint on chromosome 2. However, OGM redefined the translocation breakpoints by disclosing a paracentric inversion at 2q24.3 disrupting SCN1A . This combined genomic high-resolution approach allowed a fine characterization of the CGR, which involves two different chromosomes with four breakpoints. The patient's phenotype resulted from the concomitant loss of function of SCN1A and SCN2A .
Databáze: MEDLINE
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