NA17523
DNA from Fibroblast
Description:
LIG4 SYNDROME
LIGASE IV, DNA, ATP-DEPENDENT; LIG4
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Connective Tissue, Muscle, and Bone |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Arm
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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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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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 |
5.56 |
| Passage Frozen |
14 |
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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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| Gene |
LIG4 |
| Chromosomal Location |
13q22-q34 |
| Allelic Variant 1 |
601837.0003; LIG4 SYNDROME |
| Identified Mutation |
GLY469GLU; O'Driscoll et al. [Molec. Cell 8: 1175-1185, (2001)] identified a G-to-A transition at nucleotide 1406 of the LIG4 gene in patient 99P0149 with LIG4 syndrome (606593). The mutation resulted in a gly469-to-glu substitution in LIG4. The patient was compound heterozygous; the mutation in the other LIG4 allele was arg814 to ter (601837.0002). The phenotype of this patient, who was 9 years old, included microcephaly, developmental and mental delay, pancytopenia, multiple psoriasiform erythrodermatic skin patches, and atypical bone maturation. |
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| Gene |
LIG4 |
| Chromosomal Location |
13q22-q34 |
| Allelic Variant 2 |
601837.0002; LIG4 SYNDROME |
| Identified Mutation |
ARG814TER; O'Driscoll et al. [Molec. Cell 8: 1175-1185, (2001)] identified a C-to-T transition at nucleotide 2440 of the LIG4 gene in 2 siblings (patients 2303 and 2304) with LIG4 syndrome (606593). The mutation resulted in a nonsense codon at amino acid 814 of the LIG4 gene. O'Driscoll et al. also identified the arg814-to-ter mutation in another patient with LIG4 syndrome (patient 99P0149) who was a compound heterozygote; the other LIG4 mutation in this patient was gly469 to glu (601837.0003). |
| Remarks |
Clinically affected; skin biopsy taken from left forearm; microcephaly, developmental and mental delay, pancytopenia, multiple psoriasiform erythrodermatic skin patches, and atypical bone maturation; ligase IV deficient; donor subject is a compound heterozygote: one allele carries a G-to-A transition at nucleotide 1406 (1406G>A) of the LIG4 gene resulting in a gly469-to-glu substitution [GLY469GLU (G469E); the other allele has a C-to-T transition at nucleotide 2440 (2440C>T), resulting in a nonsense codon at amino acid 814 [ARG814TER (R814X)]. |
| Liddiard K, Grimstead JW, Cleal K, Evans A, Baird DM, Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response NAR cancer3:zcaa044 2020 |
| PubMed ID: 33447828 |
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| Wilson PF, Nham PB, Urbin SS, Hinz JM, Jones IM, Thompson LH, Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation Mutation research683:91-7 2009 |
| PubMed ID: 19896956 |
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| Muylaert I, Elias P, Knockdown of DNA ligase IV/XRCC4 by RNA interference inhibits herpes simplex virus type I DNA replication The Journal of biological chemistry282:10865-72 2007 |
| PubMed ID: 17296606 |
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| O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P, DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell8(6):1175-85 2001 |
| PubMed ID: 11779494 |
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