NA08747
DNA from Fibroblast
Description:
IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME
DNA METHYLTRANSFERASE 3B; DNMT3B
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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 |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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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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Sample Source
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DNA from Fibroblast
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Race
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White
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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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| PDL at Freeze |
6.89 |
| Passage Frozen |
9 |
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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. |
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| Gene |
DNMT3B |
| Chromosomal Location |
20q11.2 |
| Allelic Variant 2 |
602900.0009; ICF SYNDROME |
| Identified Mutation |
IVS22AS,G>A,-11; 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 |
Instability of heterochromatin of chromosomes #1, #9, and #16 with variable combined immunodeficiency; dysmorphic facial features, developmental delay, malabsorption, and recurrent infections; see GM08714 Lymphoid; 46,XX in fibroblasts; donor subject is a compound 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; the second allele has a G>A transition within intron 22 located 11 nucleotides 5-prime of the normal splice acceptor site [IVS22AS,G>A,-11] resulting in the generation of a novel splice acceptor site and a 9-bp insertion in the processed RNA. This results in the insertion of 3 amino acids (serine, threonine, and proline) at codon 744 (744ins3). 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. |
| 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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| Weisenberger DJ, Velicescu M, Cheng JC, Gonzales FA, Liang G, Jones PA, Role of the DNA methyltransferase variant DNMT3b3 in DNA methylation. Mol Cancer Res2(1):62-72 2004 |
| PubMed ID: 14757847 |
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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 |
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