[No abstract available

The ATM (ataxia-telangiectasia mutated) protein kinase mediates early cellular responses to DNA double-strand breaks (DSBs) generated during metabolic processes or by DNA-damaging agents. ATM deficiency leads to ataxia-telangiectasia, a disease marked by lymphopenia, genomic instability and an increased predisposition to lymphoid malignancies with chromosomal translocations involving lymphocyte antigen receptor loci. ATM activates cell-cycle checkpoints and can induce apoptosis in response to DNA DSBs. However, defects in these pathways of the DNA damage response cannot fully account for the phenotypes of ATM deficiency. Here, we show that ATM also functions directly in the repair of chromosomal DNA DSBs by maintaining DNA ends in repair complexes generated during lymphocyte antigen receptor gene assembly. When coupled with the cell-cycle checkpoint and pro-apoptotic activities of ATM, these findings provide a molecular explanation for the increase in lymphoid tumours with translocations involving antigen receptor loci associated with ataxia-telangiectasia.

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Chromosome 22q11.2 deletion syndrome is a common syndrome also known as DiGeorge syndrome and velocardiofacial syndrome. It occurs in approximately 1:4000 births, and the incidence is increasing due to affected parents bearing their own affected children. The manifestations of this syndrome cross all medical specialties, and care of the children and adults can be complex. Many patients have a mild to moderate immune deficiency, and the majority of patients have a cardiac anomaly. Additional features include renal anomalies, eye anomalies, hypoparathyroidism, skeletal defects, and developmental delay. Each child's needs must be tailored to his or her specific medical problems, and as the child transitions to adulthood, additional issues will arise. A holistic approach, addressing medical and behavioral needs, can be very helpful.

Patients with the Canale-Smith syndrome have mutations in Fas, which implicates this gene in the accumulation of lymphocytes and the autoimmunity characteristic of the syndrome.

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X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes and hypogammaglobulinemia. Because the disorder is uncommon, no single institution has had sufficient numbers of patients to develop a comprehensive clinical picture of the disorder. Accordingly, a national registry of United States residents with XLA was established in 1999 to provide an updated clinical view of the disorder in a large cohort of patients. A total of 201 patients were registered by 66 physicians. The estimated birth rate for the 10-year period of 1988-1997 was 1/379,000. Infection was the most common initial clinical presentation (85%), followed by a positive family history (41%) and neutropenia (11%). Although the average age of diagnosis was younger in patients with a positive family history (mean, 2.59 yr) than in patients with a negative family history (mean, 5.37 yr) (p < 0.001), only 34.5% of patients with a positive family history at the time of their birth were diagnosed before clinical symptoms developed-that is, based on family history alone. Seventy percent of patients had at least 1 episode of otitis, 62% at least 1 episode of pneumonia, 60% at least 1 episode of sinusitis, 23% at least 1 episode of chronic/recurrent diarrhea, 21% at least 1 episode of conjunctivitis, 18% at least 1 episode of pyoderma and/or cellulitis, 11% at least 1 episode of meningitis/encephalitis, 10% at least 1 episode of sepsis, 8% at least 1 episode of septic arthritis, 6% at least 1 episode of hepatitis, and 3% at least 1 episode of osteomyelitis. Fourteen of 201 (6.9%) patients were dead at the time they were entered in the Registry. However, in a prospective 4 /4-year follow-up of living patients, only 3/80 (3.75%) patients died. Causes of death included disseminated enterovirus infection (n = 6), pulmonary insufficiency (n = 5), adenovirus infection (n = 1), sepsis (n = 1), acquired immunodeficiency disease syndrome (AIDS) (n = 1), myocarditis (n = 1), hepatitis (n = 2), and stem cell transplantation (n = 1).