Search engine for discovering works of Art, research articles, and books related to Art and Culture
ShareThis
Javascript must be enabled to continue!

Case Report: Hypomorphic Ligase 4 deficiency – a paradigm of immunodysregulation

View through CrossRef
DNA Ligase 4 is critical to nonhomologous end joining, necessary for V(D)J recombination in T and B cell development. Ligase 4 deficiency is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA Ligase 4 gene, that can lead to a wide range of phenotypes. We describe a case of Ligase 4 deficiency causing a type of T-B-NK+ atypical SCID, highlighting the clinical and immunologic manifestations. An eight-year-old female, from São Nicolau Island (Cape Verde), presented at our hospital with a history of recurrent pneumonia and suppurative otitis, multiple skin lesions attributed to fungal and bacterial infections since the age of two, and recurrent diarrhea and growth impairment, beginning at the age of four. The laboratory workup showed almost absent B cells, marked hypogammaglobulinemia, and an impaired response to protein antigens. Flow cytometry revealed normal NK and T cell counts, but with nearly absent naïve T cells and TCR-Va7 expressing T lymphocytes, and reduced proliferative responses to mitogens and antigens. An oligoclonal Vβ repertoire was identified by FACS, and PROMIDISa analysis revealed a skewed TCRa repertoire signature. A 477 PID-related genes NGS panel identified a homozygous R278H mutation in the DNA Ligase 4 gene, previously reported to cause Ligase 4 deficiency. Immunoglobulin replacement and prophylactic therapies were started while waiting for hematopoietic stem cell transplantation. She has experienced fluctuating transaminase levels. The cutaneous biopsy was suggestive of lupus pernio. She has shown recurrent inflammatory signs in her limbs, with documented tenosynovitis on ultrasound. Homozygous R278H in Ligase 4 has been linked to various ranges of manifestations in Ligase 4 deficient patients. In our report, this genotype resulted in T-B-NK+ atypical SCID, that after proper prophylaxis has a predominant autoimmune phenotype.
Title: Case Report: Hypomorphic Ligase 4 deficiency – a paradigm of immunodysregulation
Description:
DNA Ligase 4 is critical to nonhomologous end joining, necessary for V(D)J recombination in T and B cell development.
Ligase 4 deficiency is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA Ligase 4 gene, that can lead to a wide range of phenotypes.
We describe a case of Ligase 4 deficiency causing a type of T-B-NK+ atypical SCID, highlighting the clinical and immunologic manifestations.
An eight-year-old female, from São Nicolau Island (Cape Verde), presented at our hospital with a history of recurrent pneumonia and suppurative otitis, multiple skin lesions attributed to fungal and bacterial infections since the age of two, and recurrent diarrhea and growth impairment, beginning at the age of four.
The laboratory workup showed almost absent B cells, marked hypogammaglobulinemia, and an impaired response to protein antigens.
Flow cytometry revealed normal NK and T cell counts, but with nearly absent naïve T cells and TCR-Va7 expressing T lymphocytes, and reduced proliferative responses to mitogens and antigens.
An oligoclonal Vβ repertoire was identified by FACS, and PROMIDISa analysis revealed a skewed TCRa repertoire signature.
A 477 PID-related genes NGS panel identified a homozygous R278H mutation in the DNA Ligase 4 gene, previously reported to cause Ligase 4 deficiency.
Immunoglobulin replacement and prophylactic therapies were started while waiting for hematopoietic stem cell transplantation.
She has experienced fluctuating transaminase levels.
The cutaneous biopsy was suggestive of lupus pernio.
She has shown recurrent inflammatory signs in her limbs, with documented tenosynovitis on ultrasound.
Homozygous R278H in Ligase 4 has been linked to various ranges of manifestations in Ligase 4 deficient patients.
In our report, this genotype resulted in T-B-NK+ atypical SCID, that after proper prophylaxis has a predominant autoimmune phenotype.

Related Results

Hydatid Disease of The Brain Parenchyma: A Systematic Review
Hydatid Disease of The Brain Parenchyma: A Systematic Review
Abstarct Introduction Isolated brain hydatid disease (BHD) is an extremely rare form of echinococcosis. A prompt and timely diagnosis is a crucial step in disease management. This ...
Breast Carcinoma within Fibroadenoma: A Systematic Review
Breast Carcinoma within Fibroadenoma: A Systematic Review
Abstract Introduction Fibroadenoma is the most common benign breast lesion; however, it carries a potential risk of malignant transformation. This systematic review provides an ove...
VITAMIN D INSUFFICIENCY IN FOUR MAJOR HOSPITALS OF PUNJAB
VITAMIN D INSUFFICIENCY IN FOUR MAJOR HOSPITALS OF PUNJAB
Objective: To demonstrate vitamin D deficiency in the general population of Punjab Study Design: Observational, Cross-Sectional Place and Duration: Multicentre study co...
CLINICAL CHARACTERISTICS OF QI, BLOOD, YIN, YANG ACCORDING TO TRADITIONAL MEDICINE OF THE ELDERLY
CLINICAL CHARACTERISTICS OF QI, BLOOD, YIN, YANG ACCORDING TO TRADITIONAL MEDICINE OF THE ELDERLY
Background: Qi, blood, Yin and Yang are especially important elements of the human body. However, in the elderly, along with the aging, the blood and qi in the body decrease there ...
Chest Wall Hydatid Cysts: A Systematic Review
Chest Wall Hydatid Cysts: A Systematic Review
Abstract Introduction Given the rarity of chest wall hydatid disease, information on this condition is primarily drawn from case reports. Hence, this study systematically reviews t...
Hydatid Cyst of The Orbit: A Systematic Review with Meta-Data
Hydatid Cyst of The Orbit: A Systematic Review with Meta-Data
Abstarct Introduction Orbital hydatid cysts (HCs) constitute less than 1% of all cases of hydatidosis, yet their occurrence is often linked to severe visual complications. This stu...
A Novel Homozygous LCK Variant in the SH2 Domain: Understanding Null vs. Hypomorphic LCK Mutations and Immune Dysregulation
A Novel Homozygous LCK Variant in the SH2 Domain: Understanding Null vs. Hypomorphic LCK Mutations and Immune Dysregulation
Background The lymphocyte-specific protein tyrosine kinase (LCK) is a critical proximal component of T cell receptor (TCR)–mediated signaling. LCK deficiency lead...

Back to Top