Description:
BLOOM SYNDROME; BLM
RECQ PROTEIN-LIKE 3; RECQL3
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
| Class |
Syndromes with Increased Chromosome Breakage |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Ethnicity
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ASHKENAZI
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
8 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| DNA LIGASE I AND II |
Lehmann et al (Cancer Res 48:6343-6347,1988) observed normal joining of Okazaki fragments during DNA replication and that these cells were more sensitive to cell killing by Dimethyl sulfate than normal cells. Lymphoblast cells from this patient have been reported by Willis and Lindahl (NATURE 325:355-357,1987) to have 25% of normal DNA ligase I activity and normal DNA ligase II activity. The DNA ligase I activity is further described as being more heat labile than the normal enzyme. In 1989, Willis et al (Carcinogenesis 10:217-219) confirmed this observation. |
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| URACIL DNA GLYCOSYLASE |
Seal et al (Proc Natl Acad Sci USA 85:2339-2343,1988) reported that monoclonal antibody, 40.10.09, to normal uracil DNA glycosylase did not react with the uracil DNA glycosylase from this Bloom syndrome culture. |
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| Gene |
RECQL3 |
| Chromosomal Location |
15q26.1 |
| Allelic Variant 1 |
604610.0001; BLOOM SYNDROME |
| Identified Mutation |
6-BP DEL/7-BP INS; In 4 ostensibly unrelated persons of Jewish ancestry, Ellis et al. [Cell 83: 655 (1995)] found homozygosity for a 6-bp deletion/7-bp insertion at nucleotide 2281 of the BLM cDNA. Deletion of ATCTGA and insertion of TAGATTC caused the insertion of the novel codons for LDSR after amino acid 736, and after these codons there was a stop codon. Ellis et al. [Cell 83: 655 (1995)] concluded that a person carrying this deletion/insertion mutation was a founder of the Ashkenazi-Jewish population, and that nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. |
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| Gene |
RECQL3 |
| Chromosomal Location |
15q26.1 |
| Allelic Variant 2 |
604610.0001; BLOOM SYNDROME |
| Identified Mutation |
6-BP DEL/7-BP INS; In 4 ostensibly unrelated persons of Jewish ancestry, Ellis et al. [Cell 83: 655 (1995)] found homozygosity for a 6-bp deletion/7-bp insertion at nucleotide 2281 of the BLM cDNA. Deletion of ATCTGA and insertion of TAGATTC caused the insertion of the novel codons for LDSR after amino acid 736, and after these codons there was a stop codon. Ellis et al. [Cell 83: 655 (1995)] concluded that a person carrying this deletion/insertion mutation was a founder of the Ashkenazi-Jewish population, and that nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. |
| Remarks |
Clinically affected; B.S. Registry #9; birth weight = 2,000 grams; failure to thrive in infancy with vomiting and diarrhea; weight at 18 months = 3.5 kg; at age 10 years: weight = 17.3 kg (mean weight of 4 1/2 year old), height = 118 cm (mean height of 6 1/2 year old); microcephaly; congenital dwarfism; facial telangiectasias: telangiectatic erythematous spots covered the nose, the adjacent parts of the cheeks, and lower part of the forehead; bullous crusted lesions covering the vermilion of underlip; cafe-au-lait spots on right shoulder and back; normal bone age at age 10 years; photosensitivity; high-pitched voice; rectal carcinoma and basal cell carcinoma of eyelid diagnosed at age 38 years; increased sister chromatid exchange; chromosome breakage; reduced level of DNA ligase I activity; donor subject is homozygous for a 6-bp deletion/7-bp insertion [6-bp del/7-bp ins] at nucleotide 2,281 of the open reading frame of the RECQL3 gene, which results in a frameshift and a stop codon; same donor as GM03403 B-lymphocyte. |
| Zita Gál, Stavroula Boukoura, Kezia Catharina Oxe, Sara Badawi, Blanca Nieto, Lea Milling Korsholm, Sille Blangstrup Geisler, Ekaterina Dulina, Anna Vestergaard Rasmussen, Christina Dahl, Wei Lv, Huixin Xu, Xiaoguang Pan, Stefanos Arampatzis, Danai-Eleni Stratou, Panagiotis Galanos, Lin Lin, Per Guldberg, Jiri Bartek, Yonglun Luo & Dorthe H. Larsen, Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation Nature Communications: 2024 |
| PubMed ID: 39242676 |
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| Johnson JE, Cao K, Ryvkin P, Wang LS, Johnson FB, Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential Nucleic acids research38:1114-22 2009 |
| PubMed ID: 19966276 |
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| Yazdi PT, Wang Y, Zhao S, Patel N, Lee EY, Qin J, SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev16(5):571-82 2002 |
| PubMed ID: 11877377 |
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| Collister M, Lane DP, Kuehl BL, Differential expression of p53, p21waf1/cip1 and hdm2 dependent on DNA damage in Bloom's syndrome fibroblasts. Carcinogenesis19:2115-20 1998 |
| PubMed ID: 9886565 |
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| German J, Bloom's syndrome. XX. The first 100 cancers. Cancer Genet Cytogenet93:100-6 1997 |
| PubMed ID: 9062585 |
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| Lu X, Lane DP, Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell75:765-78 1993 |
| PubMed ID: 8242748 |
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| Willis AE, Spurr NK, Lindahl T, Concomitant reversion of the characteristic phenotypic properties of a cell line of Bloom's syndrome origin. Carcinogenesis10:217-9 1989 |
| PubMed ID: 2910526 |
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| Kenne K, Ljungquist S, Expression of a DNA-ligase-stimulatory factor in Bloom's syndrome cell line GM1492. Eur J Biochem174:465-70 1988 |
| PubMed ID: 3391163 |
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| Lehmann AR, Willis AE, Broughton BC, James MR, Steingrimsdottir H, Harcourt SA, Arlett CF, Lindahl T, Relation between the human fibroblast strain 46BR and cell lines representative of Bloom's syndrome. Cancer Res48:6343-7 1988 |
| PubMed ID: 3180052 |
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| Seal G, Brech K, Karp SJ, Cool BL, Sirover MA, Immunological lesions in human uracil DNA glycosylase: association with Bloom syndrome. Proc Natl Acad Sci U S A85:2339-43 1988 |
| PubMed ID: 3353381 |
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| Katzenellenbogen, A contribution to Bloom's syndrome. Arch Dermatol82:609 (1960):2339-43 1960 |
| PubMed ID: 3353381 |
| Passage Frozen |
8 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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