GM08728
LCL from B-Lymphocyte
Description:
IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME
DNA METHYLTRANSFERASE 3B; DNMT3B
APPARENTLY HEALTHY INDIVIDUAL
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Chromosome Abnormalities |
| Class |
Syndromes with Increased Chromosome Breakage |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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LCL from B-Lymphocyte
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Race
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White
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Family Member
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2
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Relation to Proband
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mother
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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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis |
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| Gene |
DNMT3B |
| Chromosomal Location |
20q11.2 |
| Allelic Variant 1 |
602900.0008; ICF SYNDROME |
| Identified Mutation |
ALA603THR; In a patient with ICF syndrome (242860), Okano et al. (1999) found compound heterozygosity for 2 mutations in the DNMT3B gene. The first was a G-to-A transition at nucleotide 1807, resulting in an ala603-to-thr substitution; this change was present in the proband and her mother. The mutation occurred in a region between motifs I and IV, within the catalytic domain of DNMT3B. The second heterozygous mutation was a G-to-A transition within intron 22, located 11 nucleotides 5-prime of the normal splice acceptor site (602900.0009). This mutation resulted in the generation of a novel splice acceptor site and a 9-bp insertion in the processed RNA, encoding 3 amino acids (serine, threonine, and proline) at codon 744. The insertion was within the conserved region of the catalytic domain, which is likely to be disrupted by the insertion of a proline residue. This mutation was de novo. |
| Remarks |
Clinically normal; normal 46,XX karyotype; affected daughter is GM08714; donor subject is an obligate heterozygote: one allele has a G>A transition at nucleotide 1807 (1807G>A) of the DNMT3B gene resulting in an Ala to Thr substitution at codon 603 [Ala603Thr (A603T)], the mutation occurring in a region between motifs I and IV within the catalytic domain of DNMT3B |
| Toubiana S1, Velasco G2, Chityat A1, Kaindl AM3, Hershtig N4, Tzur-Gilat A1, Francastel C2, Selig S1., Subtelomeric methylation distinguishes between subtypes of Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome Human Molecular Genetics: 2018 |
| PubMed ID: 30010917 |
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| Yehezkel S, Segev Y, Viegas-Péquignot E, Skorecki K, Selig S, Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions Human molecular genetics: 2008 |
| PubMed ID: 18558631 |
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| Jin B, Tao Q, Peng J, Soo HM, Wu W, Ying J, Fields CR, Delmas AL, Liu X, Qiu J, Robertson KD, DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function Human molecular genetics17:690-709 2007 |
| PubMed ID: 18029387 |
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| Rollins RA, Haghighi F, Edwards JR, Das R, Zhang MQ, Ju J, Bestor TH, Large-scale structure of genomic methylation patterns Genome research16:157-63 2005 |
| PubMed ID: 16365381 |
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| Narayan A, Tuck-Muller C, Weissbecker K, Smeets D, Ehrlich M, Hypersensitivity to radiation-induced non-apoptotic and apoptotic death in cell lines from patients with the ICF chromosome instability syndrome Mutation research456:1-15 2000 |
| PubMed ID: 11087891 |
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| Tuck-Muller CM, Narayan A, Tsien F, Smeets DF, Sawyer J, Fiala ES, Sohn OS, Ehrlich M, DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients Cytogenetics and cell genetics89:121-8 2000 |
| PubMed ID: 10894953 |
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| Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM, The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci U S A96:14412-7 1999 |
| PubMed ID: 10588719 |
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| Okano M, Bell DW, Haber DA, Li E, DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell99(3):247-57 1999 |
| PubMed ID: 10555141 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not Inactivated |
| Substrate |
None specified |
| Subcultivation Method |
dilution - add fresh medium |
| Supplement |
- |
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