Cytogenetic Monitoring in Shwachman-Diamond Syndrome

Pressato, Barbara; Valli, Roberto; Marletta, Cristina; Mare, Lydia; Montalbano, Giuseppe; Curto, Francesco Lo; Pasquali, Francesco; Maserati, Emanuela

doi:10.1097/mph.0000000000000268

Cited by 17 publications

(8 citation statements)

References 18 publications

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“…On the other hand, some reports counter the risk of myeloid malignancies in SDS patients with i(7q), indicating a good prognosis of SDS with i(7q) 9, 10. However, refractory cytopenia in SDS patients with i(7q) was described in these articles 9, 10, and the significance of i(7q) in cytopenia has not yet been clarified.…”

Section: Discussionmentioning

confidence: 97%

“…The most common abnormality of bone marrow is isochromosome (7)(q10), (i(7q)), which accounts for up to 40% of abnormalities 2. The significance of i(7q) is controversial 7, 8, 9, 10. The present report describes two male siblings with SDS, one that harbored cytogenetic abnormality of i(7q) in bone marrow and required allogeneic HCT.…”

Section: Introductionmentioning

confidence: 83%

“…However, refractory cytopenia in SDS patients with i(7q) was described in these articles 9, 10, and the significance of i(7q) in cytopenia has not yet been clarified. The clinical courses of the siblings who harbored the same compound mutations although severe cytopenia was manifested in only the sibling with i(7q) indicated that i(7q) is associated with the progression of severe bone marrow failure in SDS patients.…”

Section: Discussionmentioning

confidence: 99%

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Association of isochromosome (7)(q10) in Shwachman–Diamond syndrome with the severity of cytopenia

Shimosato

Tanoshima

Tsujimoto

et al. 2017

Clinical Case Reports

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Association of isochromosome (7)(q10) in Shwachman–Diamond syndrome with the severity of cytopenia

Shimosato

Tanoshima

Tsujimoto

et al. 2017

Clinical Case Reports

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“…In general, these data indicate that patients with a high proportion of cells containing del (20)(q) show a WT expression pattern similar to healthy controls in the absence of further changes that may modify the pattern. The positive prognostic role of del (20)(q) would be a consequence of this type of rescue mechanism [8, 9], although it would be limited to cases with a high proportion of abnormal cells [22].…”

Section: Discussionmentioning

confidence: 99%

Microarray expression studies on bone marrow of patients with Shwachman-Diamond syndrome in relation to deletion of the long arm of chromosome 20, other chromosome anomalies or normal karyotype

et al. 2020

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BackgroundClonal chromosome changes are often found in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS). The most frequent ones include an isochromosome of the long arm of chromosome 7, i (7)(q10), and an interstitial deletion of the long arm of chromosome 20, del (20)(q). These two imbalances are mechanisms of somatic genetic rescue. The literature offers few expression studies on SDS.ResultsWe report the expression analysis of bone marrow (BM) cells of patients with SDS in relation to normal karyotype or to the presence of clonal chromosome anomalies: del (20)(q) (five cases), i (7)(q10) (one case), and other anomalies (two cases). The study was performed using the microarray technique considering the whole transcriptome (WT) and three gene subsets selected as relevant in BM functions. The expression patterns of nine healthy controls and SDS patients with or without chromosome anomalies in the bone marrow showed clear differences.ConclusionsThere is a significant difference between gene expression in the BM of SDS patients and healthy subjects, both at the WT level and in the selected gene sets. The deletion del (20)(q), with the EIF6 gene consistently lost, even in patients with the smallest losses of material, changes the transcription pattern: a low proportion of abnormal cells led to a pattern similar to SDS patients without acquired anomalies, whereas a high proportion yields a pattern similar to healthy subjects. Hence, the benign prognostic value of del (20)(q). The case of i (7)(q10) showed a transcription pattern similar to healthy subjects, paralleling the positive prognostic role of this anomaly as well.

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“…48 The location of the SBDS gene within 7q led to the proposal that duplication of the SBDS gene may be beneficial. The deleted region of 20q includes the EIF6 gene, leading to the hypothesis that haploinsufficiency of EIF6 may compensate for the loss of SBDS, which functions to remove EIF6 from the nascent 60S ribosomal subunit during ribosome maturation.…”

Section: Bmf: Somatic Geneticsmentioning

confidence: 99%

Aplastic anemia and clonal evolution: germ line and somatic genetics

Shimamura

2016

Hematology

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Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF. Most germ line genetic BMF disorders are characterized by a high propensity to develop MDS or AML. Many affected patients lack the physical stigmata traditionally associated with the inherited marrow failure syndromes. Although any single inherited marrow failure disorder is rare, multiplexed genetic sequencing that allows simultaneous evaluation of marrow failure genes en masse demonstrated that, as a group, these inherited disorders compose a significant subset (5% to 10%) of patients with BMF. Early diagnosis of a germ line genetic marrow failure disorder allows individualized monitoring and tailored therapy. Recent studies of somatic variants in marrow failure revealed a high frequency of clonal hematopoiesis with the acquisition of mutations in genes associated with MDS or AML. Investigation of somatic mutations in marrow failure revealed important insights into the mechanisms promoting clonal disease but also raised additional questions. This review will focus on the evaluation and implications of germ line and somatic mutations for the development of clonal disorders in patients with BMF. Challenges and limitations of clinical genetic testing will be explored.

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Cytogenetic Monitoring in Shwachman-Diamond Syndrome

Cited by 17 publications

References 18 publications

Association of isochromosome (7)(q10) in Shwachman–Diamond syndrome with the severity of cytopenia

Association of isochromosome (7)(q10) in Shwachman–Diamond syndrome with the severity of cytopenia

Microarray expression studies on bone marrow of patients with Shwachman-Diamond syndrome in relation to deletion of the long arm of chromosome 20, other chromosome anomalies or normal karyotype

Aplastic anemia and clonal evolution: germ line and somatic genetics

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