GM17523

GM17523 Fibroblast from Skin, Arm

Description:

LIG4 SYNDROME
LIGASE IV, DNA, ATP-DEPENDENT; LIG4

Affected:

Yes

Sex:

Female

Age:

10 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Biopsy Source

Arm

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Arm

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

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)].

Characterizations

PDL at Freeze

5.56

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

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.

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).

Phenotypic Data

Remarks

Publications

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

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

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

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