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Last update 08 May 2025

LIG4 Syndrome

Last update 08 May 2025

Basic Info

Synonyms

DNA (deoxyribonucleic acid) ligase IV deficiency, DNA ligase IV deficiency, Deoxyribonucleic acid ligase IV deficiency

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Introduction

A very rare genetic disorder caused by mutation in the LIG4 gene. It is characterized by unusual facial features, microcephaly, growth and developmental delay, severe immunodeficiency, and skin abnormalities.

Clinical Trials associated with LIG4 Syndrome

DRKS00021039

/ RecruitingNot ApplicableIIT

Translational Research for Persons with Abnormal DNA Damage Response - ADDRess

Start Date08 Mar 2020

Sponsor / Collaborator-

NCT04569149

/ RecruitingNot ApplicableIIT

Primordial Registry at Nemours/A. I. duPont Hospital for Children

The goal of this registry is to collect information on individuals with forms of microcephalic primordial dwarfism. The study team hopes to learn more about these conditions and improve the care of people with it by establishing this registry.

Start Date11 Mar 2008

Sponsor / Collaborator

Nemours Children's Clinic

100 Clinical Results associated with LIG4 Syndrome

100 Translational Medicine associated with LIG4 Syndrome

0 Patents (Medical) associated with LIG4 Syndrome

Literatures (Medical) associated with LIG4 Syndrome

22 May 2024·Nucleic Acids Research

DNA-PKcs suppresses illegitimate chromosome rearrangements

Article

Author: Frock, Richard L ; Sadeghi, Cheyenne A ; Wang, Jinglong

AbstractTwo DNA repair pathways, non-homologous end joining (NHEJ) and alternative end joining (A-EJ), are involved in V(D)J recombination and chromosome translocation. Previous studies reported distinct repair mechanisms for chromosome translocation, with NHEJ involved in humans and A-EJ in mice predominantly. NHEJ depends on DNA-PKcs, a critical partner in synapsis formation and downstream component activation. While DNA-PKcs inhibition promotes chromosome translocations harboring microhomologies in mice, its synonymous effect in humans is not known. We find partial DNA-PKcs inhibition in human cells leads to increased translocations and the continued involvement of a dampened NHEJ. In contrast, complete DNA-PKcs inhibition substantially increased microhomology-mediated end joining (MMEJ), thus bridging the two different translocation mechanisms between human and mice. Similar to a previous study on Ku70 deletion, DNA-PKcs deletion in G1/G0-phase mouse progenitor B cell lines, significantly impairs V(D)J recombination and generated higher rates of translocations as a consequence of dysregulated coding and signal end joining. Genetic DNA-PKcs inhibition suppresses NHEJ entirely, with repair phenotypically resembling Ku70-deficient A-EJ. In contrast, we find DNA-PKcs necessary in generating the near-exclusive MMEJ associated with Lig4 deficiency. Our study underscores DNA-PKcs in suppressing illegitimate chromosome rearrangement while also contributing to MMEJ in both species.

01 May 2024·European Journal of Human Genetics

Expanding the phenotypic spectrum of LIG4 pathogenic variations: neuro-histopathological description of 4 fetuses with stenosis of the aqueduct

Article

Author: Nicolle, Romain ; Talhi, Naima ; Razavi, Férechté ; Loeuillet, Laurence ; Barrois, Mathilde ; Boutaud, Lucile ; Attié-Bitach, Tania ; Feresin, Agnese ; Grotto, Sarah ; Coussement, Aurélie ; Rambaud, Thomas ; Bourgon, Nicolas ; Beaujard, Marie-Paule

Severe ventriculomegaly is a rare congenital brain defect, usually detected in utero, of poor neurodevelopmental prognosis. This ventricular enlargement can be the consequence of different mechanisms: either by a disruption of the cerebrospinal fluid circulation or abnormalities of its production/absorption. The aqueduct stenosis is one of the most frequent causes of obstructive ventriculomegaly, however, fewer than 10 genes have been linked to this condition and molecular bases remain often unknown. We report here 4 fetuses from 2 unrelated families presenting with ventriculomegaly at prenatal ultra-sonography as well as an aqueduct stenosis and skeletal abnormalities as revealed by fetal autopsy. Genome sequencing identified biallelic pathogenic variations in LIG4, a DNA-repair gene responsible for the LIG4 syndrome which associates a wide range of clinical manifestations including developmental delay, microcephaly, short stature, radiation hypersensitivity and immunodeficiency. Thus, not only this report expands the phenotype spectrum of LIG4-related disorders, adding ventriculomegaly due to aqueduct stenosis, but we also provide the first neuropathological description of fetuses carrying LIG4 pathogenic biallelic variations.

15 Apr 2024·Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics

[Two cases of cytopenia associated with multiple malformations].

Article

Author: Zhu, Xiao-Fan ; Zhang, Li ; Gao, Yi-Man ; Chang, Li-Xian

The first patient, a 10-year-old girl, presented with pancytopenia and recurrent epistaxis, along with a history of repeated upper respiratory infections, café-au-lait spots, and microcephaly. Genetic testing revealed compound heterozygous mutations in the DNA ligase IV (LIG4) gene, leading to a diagnosis of LIG4 syndrome. The second patient, a 6-year-old girl, was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature, hyperpigmented skin, and hand malformations. She had a positive result from chromosome breakage test. She was diagnosed with Fanconi anemia complementation group A. Despite similar clinical presentations, the two children were diagnosed with different disorders, suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.

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LIG4 Syndrome

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