Abstract
BackgroundMosaic variegated aneuploidy (MVA) syndrome is a chromosomal instability disorder that leads to aneuploidies of different chromosomes in various tissues. Type 1 MVA (MVA1) is caused by mutations in the budding uninhibited by benzimidazoles 1 homolog beta (BUB1B) gene. The main clinical features of MVA1 syndrome are growth and mental retardation, central nervous system anomalies, microcephaly, and predisposition to cancers. There have been no reports of hematopoietic stem cell transplantation (HSCT) in MVA patients.ResultsWe report an 11-year old boy diagnosed with MVA1 syndrome. The BUB1B gene mutations c.498_505delAAACTTTA and c.1288 + 5G > A were detected using the next generation sequencing (NGS) method. The patient presented with cytopenia soon after birth, but remained stable until 9 years of age, when he developed myelodysplastic syndrome associated with monosomy of chromosome 7. Due to severe dependence on blood transfusions, a TCRαβ+/CD19+ depleted HSCT was performed from a matched unrelated donor (MUD) using a treosulfan-based reduced intensity conditioning (RIC) regimen. The engraftment occurred, and no severe toxicity was observed soon after the HSCT, but on day + 47, graft rejection was detected. It was followed by prolonged pancytopenia and sepsis with multi-organ Enterococcus faecium infection, which led to the patient’s death on day + 156 after HSCT.ConclusionsIn conclusion, we demonstrate that RIC HSCT with TCRαβ+/CD19+ depletion was well tolerated and resulted in complete hematologic recovery in our MVA1 patient, but, unfortunately, it was followed by rapid graft rejection. This fact needs to be taken into consideration for HSCT in other MVA patients.
Highlights
Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal instability disorder that leads to aneuploidies of different chromosomes in various tissues
Mosaic variegated aneuploidy (MVA) syndrome is a group of rare disorders in which chromosomal instability leads to aneuploidies of different chromosomes in various tissues
The most frequent malignancies associated with MVA syndrome are embryonal rhabdomyosarcoma, Wilms tumor, and acute lymphoid leukemia (ALL), all of which have been reported to manifest in early childhood [ [8, 9]]
Summary
Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal instability disorder that leads to aneuploidies of different chromosomes in various tissues. The main clinical features of MVA1 syndrome are growth and mental retardation, central nervous system anomalies, microcephaly, and predisposition to cancers. Mosaic variegated aneuploidy (MVA) syndrome is a group of rare disorders in which chromosomal instability leads to aneuploidies (predominantly trisomies and monosomies) of different chromosomes in various tissues. There have been only several reports of MVA1 patients with known genetic defects [1, 5, 6], and to our knowledge, there has been no experience with hematopoietic stem cell transplantation (HSCT) in these patients
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