The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Lynda Ellis - One of the best experts on this subject based on the ideXlab platform.
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Shwachman Syndrome phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar
The Journal of Pediatrics, 1999Co-Authors: Hedy Ginzberg, Melvin H. Freedman, Janey Shin, Lynda Ellis, Jodi Morrison, Yigal Dror, Leo A. Heitlinger, Mary Ann Belt, Mary Corey, Johanna M RommensAbstract:Abstract Objectives: With the use of clinical data from a large international cohort, we evaluated and compared affected siblings and isolated cases. Study design: Data from 116 families were collected, and patients conforming to our predetermined diagnostic criteria were analyzed. Phenotypic manifestations of affected siblings and singletons were compared with the use of t tests, Wilcoxon scores, and χ2 analysis. Results: Eighty-eight patients (33 female, 55 male; median age 5.20 years) fulfilled our predetermined diagnostic criteria for Shwachman Syndrome; 63 patients were isolated cases, and 25 affected siblings were from 12 multiplex families. Steatorrhea was present in 86% (57 of 66), and 91% (78 of 86) displayed a low serum trypsinogen concentration. Patients older than 4 years more often had pancreatic sufficiency. Neutropenia occurred in 98%, anemia in 42%, and thrombocytopenia in 34%. Myelodysplasia or cytogenetic abnormalities were reported in 7 patients. Short stature with normal nutritional status was a prominent feature. Conclusions: Clinical features among patients with Shwachman Syndrome varied between patients and with age. Similarities in phenotype between isolated cases and affected sibling sets support the hypothesis that Shwachman Syndrome is a single disease entity. (J Pediatr 1999;135:81-8.)
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Shwachman Syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar.
The Journal of pediatrics, 1999Co-Authors: Hedy Ginzberg, Melvin H. Freedman, Janey Shin, Lynda Ellis, Jodi Morrison, Yigal Dror, Leo A. Heitlinger, Mary Ann Belt, Mary CoreyAbstract:With the use of clinical data from a large international cohort, we evaluated and compared affected siblings and isolated cases. Data from 116 families were collected, and patients conforming to our predetermined diagnostic criteria were analyzed. Phenotypic manifestations of affected siblings and singletons were compared with the use of t tests, Wilcoxon scores, and chi2 analysis. Eighty-eight patients (33 female, 55 male; median age 5.20 years) fulfilled our predetermined diagnostic criteria for Shwachman Syndrome; 63 patients were isolated cases, and 25 affected siblings were from 12 multiplex families. Steatorrhea was present in 86% (57 of 66), and 91% (78 of 86) displayed a low serum trypsinogen concentration. Patients older than 4 years more often had pancreatic sufficiency. Neutropenia occurred in 98%, anemia in 42%, and thrombocytopenia in 34%. Myelodysplasia or cytogenetic abnormalities were reported in 7 patients. Short stature with normal nutritional status was a prominent feature. Clinical features among patients with Shwachman Syndrome varied between patients and with age. Similarities in phenotype between isolated cases and affected sibling sets support the hypothesis that Shwachman Syndrome is a single disease entity.
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Correlation of intestinal lactulose permeability with exocrine pancreatic dysfunction
The Journal of pediatrics, 1992Co-Authors: D R Mack, Peter R. Durie, Lynda Ellis, J A Flick, B J Rosenstein, J A PermanAbstract:Increased intestinal permeability to lactulose has been reported in patients with cystic fibrosis (CF). To determine whether this finding is unique to CF or whether it is related to accompanying exocrine pancreatic dysfunction, we evaluated 31 patients with CF and 10 with Shwachman Syndrome who had variable degrees of pancreatic dysfunction, together with 17 healthy control subjects. There was no significant difference in the mean urinary lactulose excretion, expressed as the percentage of dose recovered, between CF and non-CF patients with pancreatic insufficiency (2.1% +/- 1.2% and 1.9% +/- 0.8, respectively) or between CF and non-CF patients with pancreatic sufficiency (0.6% +/- 0.5% and 0.6% +/- 0.3%, respectively). However, there was a significant difference in mean lactulose excretion between the pancreatic-insufficient and the pancreatic-sufficient patients (both CF and non-CF groups; p less than 0.001 and p less than 0.013, respectively). We further analyzed the results from 26 of the 41 patients (16 patients with CF and 10 non-CF patients) with pancreatic dysfunction who had previously undergone quantitative pancreatic function testing. A nonlinear, inverse relationship was found between urinary lactulose excretion and exocrine pancreatic function determined by duodenal trypsin output. These data confirm a direct relationship between intestinal lactulose permeability and the degree of exocrine pancreatic dysfunction, unrelated to the cause of the pancreatic disease.
F. Poli - One of the best experts on this subject based on the ideXlab platform.
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The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman Syndrome
Leukemia, 2009Co-Authors: A Minelli, F. Poli, E Maserati, E Nicolis, M Zecca, L Sainati, D Longoni, F Lo Curto, G Menna, E De PaoliAbstract:Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk to develop myelodysplastic Syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.
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the isochromosome i 7 q10 carrying c 258 2t c mutation of the sbds gene does not promote development of myeloid malignancies in patients with Shwachman Syndrome
Leukemia, 2009Co-Authors: Antonella Minelli, Emanuela Maserati, Marco Zecca, Giuseppe Menna, Laura Sainati, F. Poli, E Nicolis, D Longoni, Lo F Curto, E De PaoliAbstract:Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk to develop myelodysplastic Syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.
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Shwachman Syndrome as mutator phenotype responsible for myeloid dysplasia neoplasia through karyotype instability and chromosomes 7 and 20 anomalies
Genes Chromosomes and Cancer, 2006Co-Authors: Emanuela Maserati, Barbara Pressato, Roberto Valli, Antonella Minelli, Barbara Crescenzi, Maurizio Stefanelli, Giuseppe Menna, Laura Sainati, F. Poli, Claudio PanarelloAbstract:An investigation of 14 patients with Shwachman Syndrome (SS), using standard and molecular cytogenetic methods and molecular genetic techniques, showed that (1) the i(7)(q10) is not, or not always, an isochromosome but may arise from a more complex mechanism, retaining part of the short arm; (2) the i(7)(q10) has no preferential parental origin; (3) clonal chromosome changes, such as chromosome 7 anomalies and del(20)(q11), may be present in the bone marrow (BM) for a long time without progressing to myelodysplastic Syndrome (MDS)/acute myeloid leukemia (AML); (4) the del(20)(q11) involves the minimal region of deletion typical of MDS/AML; (5) the rate of chromosome breaks is not significantly higher than in controls, from which it is concluded that SS should not be considered a breakage Syndrome; (6) a specific kind of karyotype instability is present in SS, with chromosome changes possibly found in single cells or small clones, often affecting chromosomes 7 and 20, in the BM. Hence, we have confirmed our previous hypothesis that the SS mutation itself implies a mutator effect that is responsible for MDS/AML through these specific chromosome anomalies. This conclusion supports the practice of including cytogenetic monitoring in the follow-up of SS patients.
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Shwachman Syndrome as mutator phenotype responsible for myeloid dysplasia/neoplasia through karyotype instability and chromosomes 7 and 20 anomalies.
Genes chromosomes & cancer, 2005Co-Authors: Emanuela Maserati, Barbara Pressato, Roberto Valli, Antonella Minelli, Barbara Crescenzi, Maurizio Stefanelli, Giuseppe Menna, Laura Sainati, F. Poli, Claudio PanarelloAbstract:An investigation of 14 patients with Shwachman Syndrome (SS), using standard and molecular cytogenetic methods and molecular genetic techniques, showed that (1) the i(7)(q10) is not, or not always, an isochromosome but may arise from a more complex mechanism, retaining part of the short arm; (2) the i(7)(q10) has no preferential parental origin; (3) clonal chromosome changes, such as chromosome 7 anomalies and del(20)(q11), may be present in the bone marrow (BM) for a long time without progressing to myelodysplastic Syndrome (MDS)/acute myeloid leukemia (AML); (4) the del(20)(q11) involves the minimal region of deletion typical of MDS/AML; (5) the rate of chromosome breaks is not significantly higher than in controls, from which it is concluded that SS should not be considered a breakage Syndrome; (6) a specific kind of karyotype instability is present in SS, with chromosome changes possibly found in single cells or small clones, often affecting chromosomes 7 and 20, in the BM. Hence, we have confirmed our previous hypothesis that the SS mutation itself implies a mutator effect that is responsible for MDS/AML through these specific chromosome anomalies. This conclusion supports the practice of including cytogenetic monitoring in the follow-up of SS patients.
Peter R. Durie - One of the best experts on this subject based on the ideXlab platform.
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Shwachman Syndrome: Exocrine pancreatic dysfunction and variable phenotypic expression
Gastroenterology, 1996Co-Authors: Mack, Gg Forstner, M. Wilschanski, Melvin H. Freedman, Peter R. DurieAbstract:BACKGROUND & AIMS: Shwachman Syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman Syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman Syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602)
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Pathophysiology of the pancreatic defect in Johanson-Blizzard Syndrome: A disorder of acinar development†
The Journal of pediatrics, 1994Co-Authors: Nicola L. Jones, Pamela M. Hofley, Peter R. DurieAbstract:We compared pancreatic acinar and ductal secretion in two patients with Johanson-Blizzard Syndrome, age-matched control subjects, and patients with other primary pancreatic diseases. Patients with Johanson-Blizzard Syndrome had preservation of ductular output of fluid and electrolytes, as in patients with Shwachman Syndrome but differing from those with cystic fibrosis, who have a primary ductular defect. They also had decreased acinar secretion of trypsin, colipase and total lipase, and low serum immunoreactive trypsinogen levels, consistent with a primary acinar cell defect.
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Correlation of intestinal lactulose permeability with exocrine pancreatic dysfunction
The Journal of pediatrics, 1992Co-Authors: D R Mack, Peter R. Durie, Lynda Ellis, J A Flick, B J Rosenstein, J A PermanAbstract:Increased intestinal permeability to lactulose has been reported in patients with cystic fibrosis (CF). To determine whether this finding is unique to CF or whether it is related to accompanying exocrine pancreatic dysfunction, we evaluated 31 patients with CF and 10 with Shwachman Syndrome who had variable degrees of pancreatic dysfunction, together with 17 healthy control subjects. There was no significant difference in the mean urinary lactulose excretion, expressed as the percentage of dose recovered, between CF and non-CF patients with pancreatic insufficiency (2.1% +/- 1.2% and 1.9% +/- 0.8, respectively) or between CF and non-CF patients with pancreatic sufficiency (0.6% +/- 0.5% and 0.6% +/- 0.3%, respectively). However, there was a significant difference in mean lactulose excretion between the pancreatic-insufficient and the pancreatic-sufficient patients (both CF and non-CF groups; p less than 0.001 and p less than 0.013, respectively). We further analyzed the results from 26 of the 41 patients (16 patients with CF and 10 non-CF patients) with pancreatic dysfunction who had previously undergone quantitative pancreatic function testing. A nonlinear, inverse relationship was found between urinary lactulose excretion and exocrine pancreatic function determined by duodenal trypsin output. These data confirm a direct relationship between intestinal lactulose permeability and the degree of exocrine pancreatic dysfunction, unrelated to the cause of the pancreatic disease.
Emanuela Maserati - One of the best experts on this subject based on the ideXlab platform.
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the isochromosome i 7 q10 carrying c 258 2t c mutation of the sbds gene does not promote development of myeloid malignancies in patients with Shwachman Syndrome
Leukemia, 2009Co-Authors: Antonella Minelli, Emanuela Maserati, Marco Zecca, Giuseppe Menna, Laura Sainati, F. Poli, E Nicolis, D Longoni, Lo F Curto, E De PaoliAbstract:Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk to develop myelodysplastic Syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.
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Monitoring the isochromosome i(7)(q10) in the bone marrow of patients with Shwachman Syndrome by real-time quantitative PCR.
Journal of pediatric hematology oncology, 2007Co-Authors: Giovanni Porta, E Mattarucchi, Emanuela Maserati, Barbara Pressato, Roberto Valli, Cristina Morerio, Marco Zecca, Claudio Panarello, Franco Locatelli, Francesco Lo CurtoAbstract:Clonal chromosome anomalies may be found in the bone marrow (BM) of patients with Shwachman Syndrome, who are at risk to develop myelodysplastic Syndromes and/or acute myeloid leukemias. In particular, an isochromosome i(7)(q10) is frequent, and is usually monitored by chromosome analyses. We tested an approach by real-time quantitative polymerase chain reaction (RQ-PCR) on a chromosome 7 polymorphism. Five DNA samples of 2 Shwachman Syndrome patients with clonal i(7)(q10) in the BM were used. Both were heterozygous for the diallelic indel polymorphism MID1064, which maps in 7q35. The percentage of i(7)(q10)-positive cells was extrapolated from the ratio of the 2 alleles measured by means of an allele-specific RQ-PCR assay. The results were compared with cytogenetic analyses on the same material used for RQ-PCR. In 1 patient, the RQ-PCR results matched well with those of chromosome analyses, whereas in the other one RQ-PCR showed that around 40% of the BM cells were abnormal, while they resulted to be nearly 80% with conventional monitoring assays. As the results obtained by RQ-PCR refer to the DNA of around 128,000 BM cells, our method proved to be feasible and more efficient in the quantitative evaluation of the i(7)(q10)-positive clone than conventional ones.
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Shwachman Syndrome as mutator phenotype responsible for myeloid dysplasia neoplasia through karyotype instability and chromosomes 7 and 20 anomalies
Genes Chromosomes and Cancer, 2006Co-Authors: Emanuela Maserati, Barbara Pressato, Roberto Valli, Antonella Minelli, Barbara Crescenzi, Maurizio Stefanelli, Giuseppe Menna, Laura Sainati, F. Poli, Claudio PanarelloAbstract:An investigation of 14 patients with Shwachman Syndrome (SS), using standard and molecular cytogenetic methods and molecular genetic techniques, showed that (1) the i(7)(q10) is not, or not always, an isochromosome but may arise from a more complex mechanism, retaining part of the short arm; (2) the i(7)(q10) has no preferential parental origin; (3) clonal chromosome changes, such as chromosome 7 anomalies and del(20)(q11), may be present in the bone marrow (BM) for a long time without progressing to myelodysplastic Syndrome (MDS)/acute myeloid leukemia (AML); (4) the del(20)(q11) involves the minimal region of deletion typical of MDS/AML; (5) the rate of chromosome breaks is not significantly higher than in controls, from which it is concluded that SS should not be considered a breakage Syndrome; (6) a specific kind of karyotype instability is present in SS, with chromosome changes possibly found in single cells or small clones, often affecting chromosomes 7 and 20, in the BM. Hence, we have confirmed our previous hypothesis that the SS mutation itself implies a mutator effect that is responsible for MDS/AML through these specific chromosome anomalies. This conclusion supports the practice of including cytogenetic monitoring in the follow-up of SS patients.
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Shwachman Syndrome as mutator phenotype responsible for myeloid dysplasia/neoplasia through karyotype instability and chromosomes 7 and 20 anomalies.
Genes chromosomes & cancer, 2005Co-Authors: Emanuela Maserati, Barbara Pressato, Roberto Valli, Antonella Minelli, Barbara Crescenzi, Maurizio Stefanelli, Giuseppe Menna, Laura Sainati, F. Poli, Claudio PanarelloAbstract:An investigation of 14 patients with Shwachman Syndrome (SS), using standard and molecular cytogenetic methods and molecular genetic techniques, showed that (1) the i(7)(q10) is not, or not always, an isochromosome but may arise from a more complex mechanism, retaining part of the short arm; (2) the i(7)(q10) has no preferential parental origin; (3) clonal chromosome changes, such as chromosome 7 anomalies and del(20)(q11), may be present in the bone marrow (BM) for a long time without progressing to myelodysplastic Syndrome (MDS)/acute myeloid leukemia (AML); (4) the del(20)(q11) involves the minimal region of deletion typical of MDS/AML; (5) the rate of chromosome breaks is not significantly higher than in controls, from which it is concluded that SS should not be considered a breakage Syndrome; (6) a specific kind of karyotype instability is present in SS, with chromosome changes possibly found in single cells or small clones, often affecting chromosomes 7 and 20, in the BM. Hence, we have confirmed our previous hypothesis that the SS mutation itself implies a mutator effect that is responsible for MDS/AML through these specific chromosome anomalies. This conclusion supports the practice of including cytogenetic monitoring in the follow-up of SS patients.
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Isochromosome (7)(q10) in Shwachman Syndrome without MDS/AML and role of chromosome 7 anomalies in myeloproliferative disorders.
Cancer genetics and cytogenetics, 2000Co-Authors: Emanuela Maserati, Antonella Minelli, Carla Olivieri, Livia Bonvini, Antonietta Marchi, Mauro Bozzola, Cesare Danesino, Susi Scappaticci, Francesco PasqualiAbstract:Shwachman Syndrome (SS) is an autosomal recessive disorder in which bone marrow dysfunction is observed, with development of myelodysplastic Syndromes (MDS) and acute myeloid leukemias (AML) in up to one third of the cases. Inconclusive data are available as to increased chromosome breakage in SS, while chromosome 7 anomalies, and often an isochromosome (7)(q10), are frequent in cases with MDS/AML. We report on the consistent presence of an i(7)(q10) in the bone marrow and blood lymphocytes in one of two sisters affected with SS without any clinical or cytological signs of MDS/AML. Thus, this patient was either a case of constitutional mosaicism for the i(7)(q10), or this had to be acquired in a nondysplastic and non-neoplastic marrow clone. DNA polymorphism analysis demonstrated the paternal origin of the i(7q). We postulate that the SS mutation acts as a mutator gene, and causes karyotype instability; abnormal clones would thus arise in the marrow, and chromosome 7 anomalies, i(7q) in particular, will in turn lead to MDS/AML. If this interpretation is correct, it would be also an indication to consider chromosome 7 anomalies in general, out of SS, as primary changes in MDS/AML pathogenesis.
E De Paoli - One of the best experts on this subject based on the ideXlab platform.
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The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman Syndrome
Leukemia, 2009Co-Authors: A Minelli, F. Poli, E Maserati, E Nicolis, M Zecca, L Sainati, D Longoni, F Lo Curto, G Menna, E De PaoliAbstract:Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk to develop myelodysplastic Syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.
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the isochromosome i 7 q10 carrying c 258 2t c mutation of the sbds gene does not promote development of myeloid malignancies in patients with Shwachman Syndrome
Leukemia, 2009Co-Authors: Antonella Minelli, Emanuela Maserati, Marco Zecca, Giuseppe Menna, Laura Sainati, F. Poli, E Nicolis, D Longoni, Lo F Curto, E De PaoliAbstract:Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk to develop myelodysplastic Syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.
