Immunodeficiency 96 is an immune deficiency syndrome associated with mutation in the LIG1 gene. It is caused by a homozygous or compound heterozygous mutation in the LIG1 gene (126391) on chromosome 19q13. The gene encodes a member of the ATP-dependent DNA ligase protein family.
Ligases are enzymes that catalyze the joining of two molecules with simultaneous hydrolysis of the diphosphate bond in ATP or a similar triphosphate.
Webster et al (1982) reported a girl with growth retardation, a complex immunodeficiency, and increased cellular sensitivity to DNA-damaging agents. Furthermore, recurrent middle ear and chest infections occurred, resulting in poor hearing and bronchiectasis. Other features included sun sensitivity, an elfin appearance, absence of secondary sexual characteristics at puberty, and delayed bone age. At age 17, pigmented spots appeared on her skin, mainly on the limbs. Teleangiectasia also appeared on the bulbar conjunctivae. Laboratory investigations revealed persistent erythrocyte macrocytosis, low serum IgA and IgG levels, progressive lymphopenia with absent proliferative T-cell responses in vitro, increasing neutropenia, and hepatosplenomegaly with possible lymphoma. After a severe cutaneous herpes zoster infection, her condition worsened and she died at the age of 19 years from pneumonia....
Maffucci et al (2018) reported 5 patients from 3 unrelated families with IMD96. Four patients were between 3 and 6 years old, and one was 19 years old. In them, variable recurrent infections began in infancy or early childhood and were associated with hypogammaglobulinemia. The infections were mainly respiratory, although diarrhea was also reported, and the infectious agents were usually viral in nature, including adenovirus, rhinovirus, RSV, rotavirus, and herpes zoster. Patient 3 had oral candidiasis and urinary tract infections. Two siblings (P3 and P4) born to consanguineous Sudanese parents (clan C) had severe anemia requiring blood transfusions and multicystic dysplastic kidneys.
Laboratory tests revealed hypogammaglobulinemia, low B-cell counts, erythrocyte macrocytosis, and decreased absolute numbers of CD3+ T cells with increased numbers of gamma delta T cells. P1 and P2 were diagnosed with common variable immunodeficiency(CVID), and P3 and P4 were diagnosed with severe combined immunodeficiency (SCID). P3 and P4 underwent hematopoietic stem cell transplantation; the other patients were treated with Ig substitution. Overall, growth and development were normal.