Two children are reported with bone marrow (BM) failure but without a precise diagnosis. Patient n. 1 is a 3-year-old female with a severe anaemia associated with several dysmorphic/malformative symptoms. The standard karyotype was normal, but array-CGH showed a 4 Mb duplication of chromosome 1 short arms of and a 2 Mb deletion of chromosome 8 long arms. The anomaly was constitutional. The lacking region of chromosome 8 included the locus RUNX1T1 which is relevant in transcription repression of several genes with a role in myelopoiesis. The expression of RUNX1T1 in the BM was down-regulated. We postulate that the chromosome imbalances are the cause of BM failure and severe anaemia, besides of all extra-haematological signs. Patient n. 2 is a female of less than one year of age with severe pancytopenia, in absence of other symptoms. The karyotype showed a constitutional change that had been already diagnosed prenatally, and that was interpreted as a balanced translocation t(2;8). No imbalances were disclosed by array-CGH. FISH with libraries and a number of BAC probes showed that the rearrangement was in fact an insertion of two adjacent portions of chromosome 2 short arms into the long arms of chromosome 8. The RUNX1T1 gene was intact, but included in the portion between the two insertions of material from chromosome 2. The expression of RUNX1T1 in BM was highly up-regulated, probably by position effects, and this was interpreted as the cause of the pancytopenia. The two cases reported here, together with other similar ones already reported by our group, demonstrate that a possible and not infrequent cause of BM failure is a chromosome anomaly, both balanced or unbalanced, either constitutional or acquired.

BONE MARROW FAILURE CONDITIONS DUE TO CHROMOSOME ANOMALIES

MASERATI, EMANUELA;VALLI, ROBERTO;FRATTINI, ANNALISA;FABBRI, MARCO;MONTALBANO, GIUSEPPE;PASQUALI, FRANCESCO
2015

Abstract

Two children are reported with bone marrow (BM) failure but without a precise diagnosis. Patient n. 1 is a 3-year-old female with a severe anaemia associated with several dysmorphic/malformative symptoms. The standard karyotype was normal, but array-CGH showed a 4 Mb duplication of chromosome 1 short arms of and a 2 Mb deletion of chromosome 8 long arms. The anomaly was constitutional. The lacking region of chromosome 8 included the locus RUNX1T1 which is relevant in transcription repression of several genes with a role in myelopoiesis. The expression of RUNX1T1 in the BM was down-regulated. We postulate that the chromosome imbalances are the cause of BM failure and severe anaemia, besides of all extra-haematological signs. Patient n. 2 is a female of less than one year of age with severe pancytopenia, in absence of other symptoms. The karyotype showed a constitutional change that had been already diagnosed prenatally, and that was interpreted as a balanced translocation t(2;8). No imbalances were disclosed by array-CGH. FISH with libraries and a number of BAC probes showed that the rearrangement was in fact an insertion of two adjacent portions of chromosome 2 short arms into the long arms of chromosome 8. The RUNX1T1 gene was intact, but included in the portion between the two insertions of material from chromosome 2. The expression of RUNX1T1 in BM was highly up-regulated, probably by position effects, and this was interpreted as the cause of the pancytopenia. The two cases reported here, together with other similar ones already reported by our group, demonstrate that a possible and not infrequent cause of BM failure is a chromosome anomaly, both balanced or unbalanced, either constitutional or acquired.
Maserati, Emanuela; Valli, Roberto; Vinti, Luciana; Frattini, Annalisa; Fabbri, Marco; De Paoli, Elena; Montalbano, Giuseppe; Locatelli, Franco; Pasquali, Francesco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2020722
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