RESUMO
Complex rearrangements of chromosomes 3 and 9 were found in a patient presenting with severe epilepsy, developmental delay, dysmorphic facial features, and skeletal abnormalities. Molecular cytogenetic analysis revealed 46,XX.ish der(9)(3qterâ3q28::9p21.1â9p22.3::9p22.3â9qter)(RP11-368G14+,RP11-299O8-,RP11-905L2++,RP11-775E6++). Her dysmorphic features are consistent with 3q29 microduplication syndrome and inv dup del(9p). Trio-based WES of the patient revealed no pathogenic single nucleotide variants causing epilepsy, but confirmed a 3q28q29 duplication involving FGF12, which encodes fibroblast growth factor 12. FGF12 positively regulates the activity of voltage-gated sodium channels. Recently, only one recurrent gain-of-function variant [NM_021032.4:c.341G>A:p.(Arg114His)] in FGF12 was found in a total of 10 patients with severe early-onset epilepsy. We propose that the patient's entire FGF12 duplication may be analogous to the gain-of-function variant in FGF12 in the epileptic phenotype of this patient.
Assuntos
Transtornos Cromossômicos/genética , Duplicação Cromossômica/genética , Fatores de Crescimento de Fibroblastos/genética , Transtornos do Neurodesenvolvimento/genética , Espasmos Infantis/genética , Adolescente , Deleção Cromossômica , Transtornos Cromossômicos/fisiopatologia , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 9 , Variações do Número de Cópias de DNA , Feminino , Duplicação Gênica , Humanos , Lactente , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Linhagem , Espasmos Infantis/fisiopatologia , Translocação Genética , Sequenciamento do ExomaRESUMO
Mixed-lineage leukemia (MLL) rearrangements are commonly observed in childhood acute lymphoblastic and myeloid leukemia, as well as therapy-related leukemia. However, the occurrence of MLL rearrangements in acute megakaryoblastic leukemia (AMKL) is very rare. We report a pediatric case of AMKL with the MLL-AF4 fusion transcript. MLL-AF4 is derived from t(4;11)(q21:q23) and occurs exclusively in B-cell lineage leukemia. To our knowledge, MLL-AF4 as well as t(4;11)(q21:q23) has not been reported in adult and childhood AMKL. Thus, our case provides new insight into the molecular mechanisms of MLL-AF4-associated leukemia.
