Contributions
Abstract: PB1830
Type: Publication Only
Background
Neutropenia is defined as an absolute neutrophil count (ANC) < 1500 cells/mmc, can be acquired or inherited (autosomal dominant). The latter is rare and may be mild or severe, some forms may be associated with a malignant transformation in Acute Myeloid Leukemia and Myelodisplastic Syndrome. A fragile site on chromosome 16 associated to severe familiar neutropenia with variable clinical severity has been described in two cases, one of which with recurrent infections.
Aims
We have identified an additional case of a familial benign chronic neutropenia with karyotype abnormalities represented by deletion and fragile site (FRA16B) on chromosome 16 at band q22.
Methods
Chromosome studies: for evidencing FRA16B, 16q22.1, DAPI colture was used. Molecular studies: Array comparative genomic hybridization (a-CGH) was performed using Agilent SurePrint G3 Human 4x180K kit. Molecular analysis of ELANE gene (19p13.3) was performed
Results
A 35 years old Caucasian female presented with neutropenia known since the age of 15 years old with average values of neutrophils of 500/mmc. Bone marrow (BM) was normal 25 yrs before. No history of recurrent infections was reported. Hepatosplenomegaly or lymphadenopathy were absent. Blood analysis showed hemoglobin 12 g/dl, white blood cells 2000/mmc, neutrophils 640/mmc, lymphocytes 1190/mmc, monocytes 120/mmc and platelets 334.000/mmc. Screening tests for autoimmunity and anti-neutrophil antibodies (direct and indirect granulocyte immunofluorescence test; GIFT method), antiphospholipid antibodies, HIV, HCV and HBV were negative. Coagulation tests were normal. BM aspirate and biopsy resulted normal. At the age of 37 and 38 years old, the patient experienced severe pneumonia responding to antibiotic intravenous therapy with normal neutrophils and increased inflammatory markers. Karyotype on bone marrow sample evidenced the presence of a del(16)(q22) in 12 out of 20 examined metaphases. Unstimulated peripheral blood karyotype evidenced the presence of a cells population (~ 35%) with the same fragile site FRA16B (16q22.1). ArrayCGH analysis of patient was normal. No mutations in ELANE gene were detected. Due the heritability of fragile site a constitutional study of her family was performed. The patient's mother, 74 years old, had a severe neutropenia with neutrophils 500/mmc, without recurrent infections. Cytogenetic analysis on peripheral blood uncultured and coltured with fragile site inducting factors showed fra(16)(q22). The 52 years old brother had a mild neutropenia with neutrophils 1500/mmc. And the fra(16) was detected in PB only after culture with fragile site inducting factors. The patient’s father and sister showed normal blood count, with a normal karyotype
Conclusion
We describe a family that presents the simultaneous occurrence of FRA16B (16q22.1) and neutropenia in three of its members (the patient, the mother and one of two siblings). In this family, the presence of FRA16B (16q22.1) correlated specifically with neutropenia, that, interestingly, was deeper in those members (the patient and the mother) in which the fragile site was evident without the need of fragile site inducing factors culture. Even it is not possible to substantiate a causative role of FRA16B (16q22.1) in familiar neutropenia, the family described here prompts further studies to explore the possibility that this association may represent a subset of familiar neutropenias with specific, albeit not yet unraveled, genetic lesions.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Cytogenetic abnormalities, neutropenia
Abstract: PB1830
Type: Publication Only
Background
Neutropenia is defined as an absolute neutrophil count (ANC) < 1500 cells/mmc, can be acquired or inherited (autosomal dominant). The latter is rare and may be mild or severe, some forms may be associated with a malignant transformation in Acute Myeloid Leukemia and Myelodisplastic Syndrome. A fragile site on chromosome 16 associated to severe familiar neutropenia with variable clinical severity has been described in two cases, one of which with recurrent infections.
Aims
We have identified an additional case of a familial benign chronic neutropenia with karyotype abnormalities represented by deletion and fragile site (FRA16B) on chromosome 16 at band q22.
Methods
Chromosome studies: for evidencing FRA16B, 16q22.1, DAPI colture was used. Molecular studies: Array comparative genomic hybridization (a-CGH) was performed using Agilent SurePrint G3 Human 4x180K kit. Molecular analysis of ELANE gene (19p13.3) was performed
Results
A 35 years old Caucasian female presented with neutropenia known since the age of 15 years old with average values of neutrophils of 500/mmc. Bone marrow (BM) was normal 25 yrs before. No history of recurrent infections was reported. Hepatosplenomegaly or lymphadenopathy were absent. Blood analysis showed hemoglobin 12 g/dl, white blood cells 2000/mmc, neutrophils 640/mmc, lymphocytes 1190/mmc, monocytes 120/mmc and platelets 334.000/mmc. Screening tests for autoimmunity and anti-neutrophil antibodies (direct and indirect granulocyte immunofluorescence test; GIFT method), antiphospholipid antibodies, HIV, HCV and HBV were negative. Coagulation tests were normal. BM aspirate and biopsy resulted normal. At the age of 37 and 38 years old, the patient experienced severe pneumonia responding to antibiotic intravenous therapy with normal neutrophils and increased inflammatory markers. Karyotype on bone marrow sample evidenced the presence of a del(16)(q22) in 12 out of 20 examined metaphases. Unstimulated peripheral blood karyotype evidenced the presence of a cells population (~ 35%) with the same fragile site FRA16B (16q22.1). ArrayCGH analysis of patient was normal. No mutations in ELANE gene were detected. Due the heritability of fragile site a constitutional study of her family was performed. The patient's mother, 74 years old, had a severe neutropenia with neutrophils 500/mmc, without recurrent infections. Cytogenetic analysis on peripheral blood uncultured and coltured with fragile site inducting factors showed fra(16)(q22). The 52 years old brother had a mild neutropenia with neutrophils 1500/mmc. And the fra(16) was detected in PB only after culture with fragile site inducting factors. The patient’s father and sister showed normal blood count, with a normal karyotype
Conclusion
We describe a family that presents the simultaneous occurrence of FRA16B (16q22.1) and neutropenia in three of its members (the patient, the mother and one of two siblings). In this family, the presence of FRA16B (16q22.1) correlated specifically with neutropenia, that, interestingly, was deeper in those members (the patient and the mother) in which the fragile site was evident without the need of fragile site inducing factors culture. Even it is not possible to substantiate a causative role of FRA16B (16q22.1) in familiar neutropenia, the family described here prompts further studies to explore the possibility that this association may represent a subset of familiar neutropenias with specific, albeit not yet unraveled, genetic lesions.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Cytogenetic abnormalities, neutropenia