Abstrakt
Introduction: RBFOX1, one of the largest genes, is located in chromosomal region 16p13.3 and encodes protein that plays role as a splicing factor. This gene / RBFOX1 is responsible for positive and also negative regulation of alternative splicing of pre-mRNA and is expressed in heart, muscles and central nervous system, especially in neurons.
Mutations and intragenic deletions (exonic mainly) of RBFOX1 were detected in patients with neurodevelopmental disorders (intellectual disability, autism spectrum disorder, epilepsy) and neuropsychiatric diseases (schizophrenia, bipolar disorder). Materials, methods: We present four patients referred to genetic testing due to variety of neurodevelopmental problems.
DNA was extracted from peripheral blood and analyzed by array-CGH (aCGH) platform SurePrint CGH 8x60K G3 ISCA v.2 and the CytoGenomics software (Agilent Technologies). Results: aCGH analysis revealed intronic duplication of RBFOX1 gene in all cases.
We identified two identical, 25 kb duplications, encompassing only intron 2, and two bigger duplications (48 kb; 80kb) localized in intron 4. In two cases, additional aberration was detected - duplication of region 3p13 and 6q26 in one patient and mutation in MEF2C (c.44G>A p.(Arg15His)) in other patient.
Conclusion: While the mutations and intragenic deletions of RBFOX1 are known to be associated with neurodevelopmental disorders, the intragenic or whole gene duplications are still topic of discussion. There is also hypothesis that duplications are (thought to be) a risk factors rather than a cause of disease, especially in combination with other factors (second-hit model, environmental factors, etc.).
Up to date, there is limited number of published cases with these types of aberrations of RBFOX1. We report four new patients with neurodevelopmental disorders who carry the intronic duplication of RBFOX1.
Supported by: 00064203, NF-CZ11-PDP-3-003-2014, AZV17-29423A, AZV NU20-04-00279