Papers by Arleen Auerbach
Human Mutation, 2009
Bookmarks Related papers MentionsView impact
British Journal of Haematology, 2005
Bookmarks Related papers MentionsView impact
British Journal of Haematology, 2005
Bookmarks Related papers MentionsView impact
Genomics, 1997
Bookmarks Related papers MentionsView impact
Journal of the National Cancer Institute, Oct 14, 2003
Bookmarks Related papers MentionsView impact
JNCI Journal of the National Cancer Institute, 2003
Bookmarks Related papers MentionsView impact
Proceedings of the National Academy of Sciences, 2001
Somatic mosaicism has been observed previously in the lymphocyte population of patients with Fanc... more Somatic mosaicism has been observed previously in the lymphocyte population of patients with Fanconi anemia (FA). To identify the cellular origin of the genotypic reversion, we examined each lymphohematopoietic and stromal cell lineage in an FA patient with a 2815–2816ins19 mutation in FANCA and known lymphocyte somatic mosaicism. DNA extracted from individually plucked peripheral blood T cell colonies and marrow colony-forming unit granulocyte–macrophage and burst-forming unit erythroid cells revealed absence of the maternal FANCA exon 29 mutation in 74.0%, 80.3%, and 86.2% of colonies, respectively. These data, together with the absence of the FANCA exon 29 mutation in Epstein–Barr virus-transformed B cells and its presence in fibroblasts, indicate that genotypic reversion, most likely because of back mutation, originated in a lymphohematopoietic stem cell and not solely in a lymphocyte population. Contrary to a predicted increase in marrow cellularity resulting from reversion in ...
Bookmarks Related papers MentionsView impact
Nature Genetics, 1996
Bookmarks Related papers MentionsView impact
Nature Genetics, 2005
Bookmarks Related papers MentionsView impact
Nature Genetics, 2005
Bookmarks Related papers MentionsView impact
Nature Genetics, 2005
Bookmarks Related papers MentionsView impact
Genomics, 1998
Bookmarks Related papers MentionsView impact
Blood, 2013
Key Points Application of capturing/sequencing, copy number, and RNA analysis technologies ensure... more Key Points Application of capturing/sequencing, copy number, and RNA analysis technologies ensures comprehensive molecular diagnosis of Fanconi anemia.
Bookmarks Related papers MentionsView impact
Hum Mutat, 1998
Fanconi anemia (FA) is an autosomal recessive syndrome associated with hypersensitivity to DNA cr... more Fanconi anemia (FA) is an autosomal recessive syndrome associated with hypersensitivity to DNA cross-linking agents and predisposition to neoplasia. Eight complementation groups (A-H) have been described, but the only FA genes cloned so far are FAC and FAA. We have recently identified 40 different germline mutations, including microdeletions, microinsertions, and point mutations in genomic DNA from 97 FA patients from the International Fanconi Anemia Registry (IFAR) by single-strand conformational polymorphism (SSCP) analysis. Interestingly, only one mutant allele was identified in many of these patients. Haplotype analysis with intragenic polymorphisms, as well as cDNA analysis of some patients suggested the presence of large deletions that would not be detected by SSCP analysis. In this study, we report the occurrence of Alu-mediated genomic deletions in FAA. Two different deletions of 1.2 kb and 1.9 kb were found. Both deletions include exons 16 and 17 and remove a 156-bp segment from the transcript causing a shorter in-frame message. Sequence analysis revealed that introns 15 and 17 are rich in partial and complete Alu repeats. There are at least four head-to-tail arranged Alu elements in intron 17 and one in intron 15, all oriented in the 3'-->5' direction. Sequence analysis of the deletions showed that the 5' breakpoints occurred at different sites in the same Alu element in intron 15, while the 3' breakpoints were located in different Alu repeats in intron 17. Numerous Alu repeats are present in FAA, suggesting that Alu-mediated recombination might be an important mechanism for the generation of FAA mutations.
Bookmarks Related papers MentionsView impact
Human Mutation
Fanconi anemia (FA) is an autosomal recessive disorder that is defined by cellular hypersensitivi... more Fanconi anemia (FA) is an autosomal recessive disorder that is defined by cellular hypersensitivity to DNA cross‐linking agents, and is characterized clinically by developmental abnormalities, progressive bone‐marrow failure, and predisposition to leukemia and solid tumors. There is extensive genetic heterogeneity, with at least 11 different FA complementation groups. FA‐A is the most common group, accounting for approximately 65% of all affected individuals. The mutation spectrum of the FANCA gene, located on chromosome 16q24.3, is highly heterogeneous. Here we summarize all sequence variations (mutations and polymorphisms) in FANCA described in the literature and listed in the Fanconi Anemia Mutation Database as of March 2004, and report 61 novel FANCA mutations identified in FA patients registered in the International Fanconi Anemia Registry (IFAR). Thirty‐eight novel SNPs, previously unreported in the literature or in dbSNP, were also identified. We studied the segregation of co...
Bookmarks Related papers MentionsView impact
Cellular Therapy and Transplantation, 2010
Bookmarks Related papers MentionsView impact
Human mutation, Jan 3, 2016
Fanconi anemia (FA) is a rare inherited disorder caused by pathogenic variants in one of 19 FANC ... more Fanconi anemia (FA) is a rare inherited disorder caused by pathogenic variants in one of 19 FANC genes. FA patients display congenital abnormalities, and develop bone marrow failure, and cancer susceptibility. We identified homozygous mutations in four FA patients and, in each case, only one parent carried the obligate mutant allele. FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family respectively. Genotyping with short tandem repeat markers and single nucleotide polymorphism (SNP) arrays revealed uniparental disomy (UPD) of the entire mutation-carrying chromosome 16 in all four patients. One FANCA patient had paternal UPD, whereas FA in the other three patients resulted from maternal UPD. These are the first reported cases of UPD as a cause of FA. UPD indicates a reduced risk of having another child with FA in the family and has implications in prenatal diagnosis. This article is protected by copyright. All rights ...
Bookmarks Related papers MentionsView impact
Ash Annual Meeting Abstracts, Nov 16, 2004
Bookmarks Related papers MentionsView impact
Amer J Med Genet, 1996
We report on a child with microcephaly, small facial and body size, and immune deficiency. The ph... more We report on a child with microcephaly, small facial and body size, and immune deficiency. The phenotype is consistent with Nijmegen breakage syndrome (NBS), with additional clinical manifestations and laboratory findings not reported heretofore. Most investigations, including the results of radiation-resistant DNA synthesis, concurred with the diagnosis of NBS. Cytogenetic analysis documented abnormalities in virtually all cells examined. Along with the high frequency of breaks and rearrangements of chromosomes 7 and 14, we found breakage and monosomies involving numerous other chromosomes. Because of some variation in the clinical presentation and some unusual cytogenetic findings, we suggest that our patient may represent a new variant of Nijmegen breakage syndrome.
Bookmarks Related papers MentionsView impact
Brit J Haematol, 2008
We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA)... more We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.
Bookmarks Related papers MentionsView impact
Uploads
Papers by Arleen Auerbach