Congenital Aplastic Anemia Caused by Mutations in the <i>SBDS</i> Gene: A Rare Presentation of Shwachman-Diamond Syndrome

Kuijpers, Taco W.; Nannenberg, Eline A.; Alders, Mariëlle; Bredius, Robbert G. M.; Hennekam, Raoul C. M.

doi:10.1542/peds.2003-0651-f

Cited by 37 publications

(43 citation statements)

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“…Overt failure at birth was observed in a single of our SDS patients only. 24 Although transfusion-dependent aplastic anemia has been reported at later age during childhood and adolescence, 7,8 we did not observe any features of imminent bone marrow failure in any of the other patients with SDS. Colony formation tests (CFU-GM and BFU-E) were performed in 14 patients.…”

Section: Resultscontrasting

confidence: 48%

“…One patient was put on G-CSF (patient 7; up to 30 g/kg, 3 times a week) because of repeated infections resulting from congenital aplastic anemia. 24 The patient's response to G-CSF did not result in a significant rise in circulating neutrophil numbers, although her clinical condition improved considerably. Apart from this single case, we may conclude that the rate of infection was not strongly increased in our cohort.…”

Section: Resultsmentioning

confidence: 88%

“…As reported before, the patient with congenital anemia was on epopoietin but had a normocytic anemia without any increments in HbF compared with age control subjects. 24 Hematologic variation was observed in their blood counts ( Table 1). As known from previous reports, the neutrophil counts may fluctuate in SDS.…”

Section: Resultsmentioning

confidence: 99%

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Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship

Kuijpers

Alders

Tool

et al. 2005

Blood

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Section: Resultscontrasting

confidence: 48%

Section: Resultsmentioning

confidence: 88%

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Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship

Kuijpers

Alders

Tool

et al. 2005

Blood

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“…[17][18][19][20][21][22][23] The terminology non-malignant SC was preferred to aplastic anemia, because routine bone marrow samples from SDS patients exhibited dysgranulopoietic features or abnormalities of granulopoietic maturation. As in Fanconi anemia, the dyserythropoiesis, hyposegmentation or condensed chromatin should not be considered as a sign of myelodysplasia, 37 unless it is observed in more than 50% of the neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundPatients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. Design and MethodsOne hundred and two patients with Shwachman-Diamond syndrome, with a median followup of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20×10 9 /L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. ResultsSevere cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by nonmalignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. ConclusionsPatients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.Key words: Shwachman-Diamond syndrome, genotype, aplastic anemia, secondary leukemia, cytopenia, myelodysplasia, monosomy 7.Citation: Donadieu J, Fenneteau O, Beaupain B, Beaufils S, Bellanger F, Mahlaoui N, Lambilliotte A, Aladjidi N, Bertrand Y, Mialou V, Perot C, Michel G, Fouyssac F, Paillard C, Gandemer V, Boutard P, Schmitz J, Morali A, Leblanc T, Bellanné-Chantelot C, and Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

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“…It may however involve other organs making diagnosis difficult. SDS exceptionally presents with severe anemia, as in this child [21], and on the other hand, MRC disorders are far more frequent than SDS [22,23]. Pearson syndrome was thus initially considered in this child, since the non-specific gastrointestinal, hepatic and hematological symptoms are commonly found in MRC disorders, to variable extents [24].…”

Section: Resultsmentioning

confidence: 99%

Identification of a novel AluSx-mediated deletion of exon 3 in the SBDS gene in a patient with Shwachman–Diamond syndrome

Costa

Duque²,

Oliveira

et al. 2007

Blood Cells, Molecules, and Diseases

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Shwachman-Diamond syndrome (SDS) is caused by mutations in the SBDS gene, most of which are the result of gene conversion events involving its highly homologous pseudogene SBDSP. Here we describe the molecular characterization of the first documented gross deletion in the SBDS gene, in a 4-year-old Portuguese girl with SDS. The clinical diagnosis was based on the presence of hematological symptoms (severe anemia and cyclic neutropenia), pancreatic exocrine insufficiency and skeletal abnormalities. Routine molecular screening revealed heterozygosity for the common splicing mutation c.258 + 2T>C, and a further step-wise approach led to the detection of a large deletion encompassing exon 3, the endpoints of which were subsequently delineated at the gDNA level. This novel mutation (c.258 + 374_459 + 250del), predictably giving rise to an internally deleted polypeptide (p.Ile87_Gln153del), appears to have arisen from an excision event mediated by AluSx elements which are present in introns 2 and 3.Our case illustrates the importance of including gross deletion screening in the SDS diagnostic setting, especially in cases where only one deleterious mutation is detected by routine screening methods. In particular, deletional rearrangements involving exon 3 should be considered, since Alu sequences are known to be an important cause of recurrent mutations.

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Congenital Aplastic Anemia Caused by Mutations in the SBDS Gene: A Rare Presentation of Shwachman-Diamond Syndrome

Cited by 37 publications

References 30 publications

Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship

Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Identification of a novel AluSx-mediated deletion of exon 3 in the SBDS gene in a patient with Shwachman–Diamond syndrome

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