Cale et al. (1997) reported a child, born of consanguineous Turkish parents, who presented at age 2 months with a fever, rash, hepatosplenomegaly, lymphadenopathy, pneumonitis, and pancytopenia. Cytomegalovirus was detected in buffy coats, a liver biopsy, nasopharyngeal aspirates, ... Cale et al. (1997) reported a child, born of consanguineous Turkish parents, who presented at age 2 months with a fever, rash, hepatosplenomegaly, lymphadenopathy, pneumonitis, and pancytopenia. Cytomegalovirus was detected in buffy coats, a liver biopsy, nasopharyngeal aspirates, and urine. Laboratory investigation showed low T-cell numbers and decreased immunoglobulins with normal B-cell numbers. All nucleated hematopoietic cells had abnormal expression of CD45. Puel et al. (1998) reported a patient who presented at age 2 months with gastroesophageal reflux. Despite a Nissen fundoplication and pylorotomy, he continued to cough and had poor weight gain. He also had recurrent otitis, thrush, and a monilial diaper dermatitis. Immunologic evaluation showed elevated IgG and IgA, both of which contained paraproteins. A second unrelated patient presented at age 1 month with recurrent otitis media resistant to treatment, persistent oral moniliasis, diarrhea, fevers, and poor growth. At the age of 13 months, he developed parainfluenza type 3. Both patients had normal or elevated numbers of CD20+ B cells, greatly diminished CD3+ T cells, and normal or elevated CD16+ NK cells. Proliferation to mitogen and allogeneic cells was defective, but NK-cell killing of K562 target cells was normal. The second patient received a haploidentical bone marrow transplant, with which full immunologic reconstitution was achieved, and was clinically well more than 4 years posttransplantation. Roifman et al. (2000) reported 3 patients from a consanguineous Sicilian family with markedly reduced circulating T cells, an absence of serum Ig in spite of normal B-cell numbers, and preserved NK cell numbers and function. Although the Ig levels and NK phenotype were distinct from X-linked SCID (300400), the patients were indistinguishable clinically, with severe and persistent viral and protozoal infections. Dadi et al. (2003) reported 3 members of a kindred of Mennonite descent who had T-, B+, NK+ SCID. The proband was diagnosed immediately after birth because of 2 previous cases in the family. The proband subsequently underwent bone marrow transplantation and was alive and well, with full immune reconstitution, 3 years later. A male cousin of the proband was admitted at the age of 2 months with fever, tachypnea, and tachycardia, and died of multiorgan failure. Adenovirus was identified in stool, urine, and bronchial secretions. Another male cousin of the proband was well and thriving until 2.5 months of age, when chronic diarrhea developed. He died at 3.5 months of age with respiratory distress and liver failure. Cytomegalovirus was identified in multiple tissues obtained at autopsy. That 2 of the 3 affected infants in this kindred died from viral infections before 4 months of age was a striking demonstration of the essential role of T cells in the defense against viruses, even weakly pathogenic adenoviruses and cytomegalovirus. The number of NK cells, as determined by staining for CD56 (116930), was normal in all patients.
In 2 unrelated patients with T-, B+, NK+ SCID, Puel et al. (1998) identified mutations in the IL7R gene (146661.0001-146661.0004).
In 3 affected patients from a consanguineous Sicilian family with T-, ... - IL7R Gene In 2 unrelated patients with T-, B+, NK+ SCID, Puel et al. (1998) identified mutations in the IL7R gene (146661.0001-146661.0004). In 3 affected patients from a consanguineous Sicilian family with T-, B+, NK+ SCID, Roifman et al. (2000) identified a homozygous mutation in the IL7R gene (146661.0005). - CD45 Gene In a patient with T-, B+, NK+ SCID previously reported by Cale et al. (1997), Tchilian et al. (2001) identified a homozygous deletion in the CD45 gene (151460.0003). Roberts et al. (2012) identified a boy with CD45-deficient T-, B+, NK- SCID who was born to nonconsanguineous parents. The patient was successfully treated by maternal bone marrow transplantation at age 10 months and appeared to be phenotypically normal at age 5 years. The patient's mother was heterozygous for a lys540-to-ter (K540X; 151460.0004) mutation in the CD45 gene, but the paternal alleles exhibited no detectable mutation. The patient had no change in copy number, but loss of heterozygosity, for the entire length of chromosome 1, indicating that SCID was caused by uniparental disomy (UPD) with isodisomy of the entire maternal chromosome 1 bearing the mutant allele. Nonlymphoid cells retained UPD of the entire maternal chromosome 1. The faulty chromosome also carried mutations in 7 other genes predicted to have deleterious effects on protein function. Roberts et al. (2012) proposed that UPD should be considered in SCID and other recessive disorders, particularly when only 1 patient appears to be homozygous for an abnormal gene found in only 1 parent. - CD3D Gene In 3 affected patients from a Mennonite kindred with T-, B+, NK+ SCID, Dadi et al. (2003) identified a homozygous nonsense mutation in the CD3D gene (R68X; 186790.0001). In 2 patients with T-, B+, NK+ SCID, both from consanguineous families, de Saint Basile et al. (2004) identified homozygosity for different mutations in the CD3D gene. One patient had the previously reported R68X mutation, and the other had a C93X mutation (186970.0002). - CD3E Gene In a patient with T-, B+, NK+ SCID from a consanguineous family, de Saint Basile et al. (2004) identified a deletion mutation in the CD3E gene (186830.0003).