Haploinsufficiency of A20 with a novel mutation of deletion of exons 2-3 of TNFAIP3.
Mod Rheumatol
; 31(2): 493-497, 2021 Mar.
Article
en En
| MEDLINE
| ID: mdl-32011208
ABSTRACT
OBJECTIVES:
Haploinsufficiency of A20 (HA20) due to loss-of-function mutations of TNFAIP3 leads to an autoinflammatory disease. These mutations produce a premature termination codon in most cases of HA20. However, exon deletion has not been reported.METHODS:
Genomic DNA was extracted from the peripheral blood of the patient clinically suspected of HA20. We examined autoinflammatory disease-causing genes and performed a multiplex ligation-dependent probe amplification (MLPA) assay for copy number analysis. Next, to determine the disconnection point, genomic DNA was amplified with long-range PCR and sequenced. Finally, western blotting was carried out to measure A20 protein expression in mitogen phytohaemagglutinin (PHA)-induced T-cell blasts from the patient and a healthy volunteer.RESULTS:
Targeted next-generation sequencing found no pathogenic mutation, but copy number variation (CNV) analysis suggested a heterozygous deletion of exons 2-3. The MLPA assay and long-range PCR confirmed the mutation. Western blotting analysis indicated a marked decrease in expression of A20 protein from the patient compared to a normal control. The results showed that this deletion was a pathogenic mutation.CONCLUSION:
This study demonstrates a novel mutation resulting in a deletion of exons 2-3 of TNFAIP3. MLPA analysis is a useful initial screening method for HA20 patients.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Haploinsuficiencia
/
Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Mod Rheumatol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón