Mosaicism for FMR1 gene full mutation and intermediate allele in a female foetus: A postzygotic retraction event |
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Authors: | Susana Isabel Ferreira Luís Miguel Pires José Ferrão Joaquim Sá Armando Serra Isabel Marques Carreira |
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Institution: | 1. Laboratório de Citogenética e Genómica, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal;2. Serviço de Genética Médica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;3. Serviço de Genética e Biologia Forenses, Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. Delegação do Centro, Coimbra, Portugal;4. CIMAGO — Centro de Investigação em Meio Ambiente, Genética e Oncobiologia, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal;5. CENCIFOR — Centro Ciências Forenses, Instituto Nacional de Medicina Legal e Ciências Forenses, I.P., Coimbra, Portugal |
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Abstract: | Fragile X syndrome is caused by the expansion of an unstable CGG repeat in the 5′UTR of FMR1 gene. The occurrence of mosaicism is not uncommon, especially in male patients, whereas in females it is not so often reported. Here we report a female foetus that was subject to prenatal diagnosis, because of her mother being a premutation carrier. The foetus was identified as being a mosaic for an intermediate allele and a full mutation of FMR1 gene, in the presence of a normal allele. The mosaic status was confirmed in three different tissues of the foetus – amniotic fluid, skin biopsy and blood – the last two obtained after pregnancy termination. Karyotype analysis and X-chromosome STR markers analysis do not support the mosaicism as inheritance of both maternal alleles. Oligonucleotide array-CGH excluded an imbalance that could contain the primer binding site with a different repeat size. The obtained results give compelling evidence for a postzygotic expansion mechanism where the foetus mosaic pattern originated from expansion of the mother's premutation into a full mutation and consequent regression to an intermediate allele in a proportion of cells. These events occurred in early embryogenesis before the commitment of cells into the different tissues, as the three tested tissues of the foetus have the same mosaic pattern. The couple has a son with Fragile X mental retardation syndrome and choose to terminate this pregnancy after genetic counselling. |
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Keywords: | 5&prime UTR 5&prime unstranslated region Array-CGH array-Comparative Genomic Hybridization FMR1 Fragile X Mental Retardation 1 gene FMRP Fragile X Mental Retardation Protein IQ Intelligence Quotient PCR Polymerase Chain Reaction STR Short Tandem Repeat TP PCR Triplet Repeat Primed PCR |
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