Shwachman syndrome: Phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar

Ginzberg, Hedy; Shin, Janey; Ellis, Lynda; Morrison, Jodi; Ip, Wan; Dror, Yigal; Freedman, Melvin H.; Heitlinger, Leo A.; Belt, Mary Ann; Corey, Mary; Rommens, Johanna M.; Durie, Peter R.

doi:10.1016/s0022-3476(99)70332-x

Cited by 220 publications

(246 citation statements)

References 29 publications

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…It is interesting to note that cases 4 and 5 were siblings with same genotype, but they showed different clinical manifestations. Discordance of skeletal features in SDS had been reported previously (Mack et al 1996;Ginzberg et al 1999;Dror and Freedman 2002;Smith 2002) and Mäkitie et al (2004) recently demonstrated that the skeletal changes were variable even among patients with identical genotypes. Mutations identified to date in affected Japanese individuals from 14 families.…”

Section: Discussionmentioning

confidence: 63%

Genetic Analysis of Shwachman-Diamond Syndrome: Phenotypic Heterogeneity in Patients Carrying Identical SBDS Mutations

Kawakami

Mitsui

Kanai

et al. 2005

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Shwachman-Diamond syndrome (SDS) is a rare hereditary disorder characterized by pancreatic exocrine insufficiency, bone marrow dysfunction and skeletal changes. Recently, the cause of SDS was identified as mutations of Shwachman-BodianDiamond syndrome gene (SBDS) and most mutations are caused by gene conversion between SBDS and its highly homologous pseudogene. Clinical variations especially in skeletal and bone marrow abnormalities are well known in this syndrome. To study the relationship between SBDS mutation and its clinical features, we analyzed 9 Japanese patients including one sibling and detected the three different SBDS mutations in 7 patients: a mutation that disrupts the donor splice site of intron 2, deletes 8bp of the exon 2 and produces premature termination (258+2 T > C), a dinucleotide change that replaces a lysine at 62nd amino acid to a termination codon (183-184 TA > CT), and a 4-bp deletion that causes premature termination by frameshift (292-295 delAAAG). The 5 patients represent compound heterozygotes of the 258+2 T > C and 183-184 TA > CT mutations. One patient is a compound heterozygote of the 258+2 T > C and 292-295 delAAAG mutations, and in the remaining one case only a 258+2 T > C mutation could be detected. Thus, the 258+2 T > C and 183-184 TA > CT mutations are prevalent among Japanese patients. No mutations were found in two cases, despite the clinical features. Of the 7 patients with SBDS mutations, persistent hematologic abnormalities and skeletal changes were not observed in 3 and 2 patients, respectively. Notably, clinical variations are present even among the patients with the identical genotype: compound heterozygotes of the 258+2 T >

show abstract

Section: Discussionmentioning

confidence: 63%

Genetic Analysis of Shwachman-Diamond Syndrome: Phenotypic Heterogeneity in Patients Carrying Identical SBDS Mutations

Kawakami

Mitsui

Kanai

et al. 2005

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…1,7 We have previously shown that the cytopenia and the For personal use only. on April 4, 2019. by guest www.bloodjournal.org From hypocellular bone marrow in the disorder are not related to inhibitory factors but to faulty progenitors and a deficiency of stroma-derived stimulatory activity.…”

Section: Discussionmentioning

confidence: 99%

“…1 In brief, patients were included if they had at least one of the following criteria for exocrine pancreatic dysfunction: abnormal findings on quantitative pancreatic stimulation test, low serum cationic trypsinogen levels, abnormal findings on 72-hour fecal fat analysis plus evidence of pancreatic lipomatosis by ultrasonography or computed tomography, and at least one of these hematologic abnormalities-neutropenia, marrow granulocytic hypoplasia, hypoplastic bone marrow, or myelodysplastic syndrome. Accordingly, 11 patients were included in this study, which was conducted from February 1997 to January 1999 (Table 1).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

“…[1][2][3] Furthermore, it has been noted recently that patients with the syndrome have a marked propensity for myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML); these occur in up to one third of the patients. [1][2][3][4][5][6] The genetic or molecular defects of the disease and the factors that predispose patients to these complications are still unknown. We have previously shown that the bone marrow of patients with SDS is characterized by a decreased frequency of CD34 ϩ cells and that marrow CD34 ϩ cells have a reduced ability to form hematopoietic colonies in vitro.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway

Dror

Freedman

2001

Blood

Self Cite

112

View full text Add to dashboard Cite

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow disorder with varying cytopenias and a strong predilection to myelodysplastic syndrome (MDS) and acute myeloid leukemia. Previously, it was found that the percentage of CD34 ؉ cells in bone marrow and the in vitro colony formation from CD34 ؉ cells of patients with SDS were markedly reduced. For these reasons, and because apoptosis is central in the pathogenesis of bone marrow dysfunction in MDS, this study was initiated to delineate the role of apoptosis in the pathogenesis of the marrow failure. Eleven children with SDS were studied. Compared to normal controls, patients' marrow mononuclear cells plated in clonogenic cultures showed a significantly higher tendency to undergo apoptosis. The defect in SDS was found in patients with and without MDS. Patients showed a more prominent decrease in colony formation and increased apoptosis after preincubation with activating anti-Fas antibody. Fas expression on marrow cells from patients was significantly higher than from normal controls. The difference between patients and controls for Fas expression was also significant for the following cell fraction sub-

show abstract

“…Persistent diarrhea, malnutrition and growth failure due to fatty replacement of pancreatic acinar tissue are most prominent during infancy and improve spontaneously in up to 50 % of patients by age [9]. Mean birth weight is at the 25th percentile, however; by 6 months of age, mean weights and heights decrease below the 3rd percentile of age like our patient.…”

Section: Case Reportmentioning

confidence: 47%

Molecular Diagnosis of Shwachman-Diamond Syndrome Presenting with Pancytopenia at an Early Age: The First Report from Turkey

Gökçe

Tuncer

Çetin

et al. 2012

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

A three-month-old boy presented with growth failure, skeletal abnormalities, otitis media and pancytopenia. Exocrine pancreatic insufficiency was confirmed by low levels of fecal elastase. He was diagnosed as Shwachman-Diamond syndrome by clinical and laboratory findings. The diagnosis was confirmed by sequence analysis for SBDS gene on chromosome seven revealing compound heterozygous mutation, which are c.258?2T-C and c.183-184TA-CT. Matched unrelated donor screening for hematopoietic stem cell transplantation was initiated. Unfortunately, he died of respiratory difficulty at 5 months of age. Our case is the youngest patient whose presumptive Shwachman-Diamond syndrome diagnosis was confirmed by molecular analysis.

show abstract

Shwachman syndrome: Phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar

Cited by 220 publications

References 29 publications

Genetic Analysis of Shwachman-Diamond Syndrome: Phenotypic Heterogeneity in Patients Carrying Identical SBDS Mutations

Genetic Analysis of Shwachman-Diamond Syndrome: Phenotypic Heterogeneity in Patients Carrying Identical SBDS Mutations

Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway

Molecular Diagnosis of Shwachman-Diamond Syndrome Presenting with Pancytopenia at an Early Age: The First Report from Turkey

Contact Info

Product

Resources

About