RESUMO
INTRODUCTION: Here we present an unusual case of DNA ligase IV deficiency syndrome without dysmorphic facial findings and microcephaly complicated with Epstein-Barr virus-associated large B-cell lymphoma with the right lung involvement and a massive brain tumor lesion in a two-year-old female. METHODS: PID panel was used for sequencing 55 genes. Most genes have >98% exon coverage including splicing sites. LIG4 gene has 100% exon and splicing site coverage. This was used in Ion Torrent PGM system, the library kit was made by Agilent with Haloplex technology. The sequence analysis software was Alamut, direct sequencing of LIG4 gene was performed after NGS results. RESULT: We identified three heterozygous mutations in LIG4 gene c.2736+3delC and c.8 C>T (p.A3V) inherited from mother and c.26C>T (p.T9I) - from father after PID panel sequencing and some additional polymorphisms in ATM, NOD2 and NLRP3 genes. CONCLUSION: This case broadens the clinical spectrum of DNA ligase IV deficiency.
Assuntos
Neoplasias Encefálicas/imunologia , DNA Ligases/deficiência , Infecções por Vírus Epstein-Barr/imunologia , Síndromes de Imunodeficiência/imunologia , Neoplasias Pulmonares/imunologia , Linfoma Difuso de Grandes Células B/imunologia , Neoplasias Primárias Múltiplas/imunologia , Neoplasias Encefálicas/virologia , Pré-Escolar , DNA Ligase Dependente de ATP , DNA Ligases/genética , Feminino , Herpesvirus Humano 4 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Síndromes de Imunodeficiência/genética , Neoplasias Pulmonares/virologia , Linfoma Difuso de Grandes Células B/virologia , Mutação , Neoplasias Primárias Múltiplas/virologia , Análise de Sequência de DNARESUMO
DNA ligase IV deficiency is a rare disorder characterized by mutations in the LIG4 gene. Mutations in this gene cause a wide array of phenotypes, many of which are fatal early in life. We present an adolescent patient with heterozygous LIG4 mutations and the T-B-NK+ DNA ligase IV phenotype. Pelvic ultrasound and magnetic resonance imaging was completed to assess the patient's amenorrhea and delayed puberty, which demonstrated an atrophic cervix, distal vagina, and uterus without direct visualization of the ovaries. Early diagnosis of DNA ligase IV deficiency is important to minimize exposure to ionizing radiation from radiologic studies and preferentially utilize imaging studies that do not require ionizing radiation, such as ultrasonography and magnetic resonance imaging.