Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome)

Jawad, Abbas F.; McDonald‐McGinn, Donna M.; Zackai, Elaine H.; Sullivan, Kathleen E.

doi:10.1067/mpd.2001.118534

Cited by 237 publications

(206 citation statements)

References 51 publications

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“…This is consistent with previous observations of patients with JRA who had deletion of the long arm of chromosome 18 (5) or an unbalanced reciprocal translocation resulting in monosomy of the short arm of chromosome 18 (4). In addition, a patient with a deletion of 22q11 developed JRA in our study; this was consistent with previous findings (18).…”

Section: Discussionsupporting

confidence: 93%

Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements

Bache¹,

Nielsen²,

Rostgaard³

et al. 2007

Arthritis & Rheumatism

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Objective. Constitutional structural chromosomal rearrangements (CSCRs) have facilitated the identification of genes associated with early-onset monogenic disorders and, more recently, genes associated with common and late-onset disorders. In an attempt to find genetic clues to their etiologies, we studied the risk of autoimmune diseases in a Danish cohort of CSCR carriers.Methods. We followed up 4,866 CSCR carriers over 71,230 person-years (1980 through 2004) for autoimmune diseases recorded in the Danish Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) served as measures of the relative risk. To identify possible candidate loci for autoimmune diseases, the reported chromosomal breakpoints and deletions in CSCR carriers who developed autoimmune diseases were compared with previously suggested loci for these diseases.Results. The overall risk of any autoimmune disease among CSCR carriers was inconspicuous (SIR 1.2 [95% CI 0.95-1.5]; n ‫؍‬ 74 cases observed versus 61.3 expected), but carriers of rearrangements involving chromosomes 2, 19, and 21 were at significantly increased risk. For the specific autoimmune diseases studied, cohort members were at significantly increased risk of Dupuytren's contracture, pernicious anemia, and juvenile rheumatoid arthritis (JRA). Sixteen carriers who developed an autoimmune disease had a chromosomal breakpoint or deletion coinciding with a previously suggested locus, including deletions 18p11, 18q22, and 22q11 associated with JRA.Conclusion. CSCR carriers do not have a generalized predisposition to autoimmune diseases. However, we confirmed a number of reported susceptibility loci for JRA, and we suggest new susceptibility loci on chromosomes 5 and 11 for Dupuytren's contracture, and 19p13 as a possible shared susceptibility locus for a range of autoimmune diseases.Autoimmune diseases are a complex group of chronic diseases characterized by the loss of immune tolerance to self antigens. The etiology of most autoimmune diseases is unknown, but genetic risk factors, including the major histocompatibility complex (MHC), are believed to be involved together with environmental factors (1). The MHC and some of the non-MHC susceptibility genes are suggested to be shared by different autoimmune diseases, which might possibly explain the occasional observation of different autoimmune diseases within the same family and individuals with several different autoimmune diseases (2).To date, strategies for identifying genes associated with complex diseases have been based primarily on the mapping of susceptibility loci by linkage and association studies. The inherent difficulties of these approaches are due to the genetic heterogeneity associated with complex disorders, families with few affected members, incomplete penetrance, variable age at onset, and difficulties associated with diagnostic criteria. In monogenic disorders, a fruitful alternative approach has been to identify affected individuals with unique chromosomal rearrangements...

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Section: Discussionsupporting

confidence: 93%

Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements

Bache¹,

Nielsen²,

Rostgaard³

et al. 2007

Arthritis & Rheumatism

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“…Björk et al 45 found that 6 of 26 adult patients (23%) had low immunoglobulin levels. Autoimmune diseases, like rheumatoid diseases and idiopathic thrombocytopenia purpura, are seen in approximately 10% of patients with 22q11.2 deletion syndrome, 46 whereas no autoimmune diseases were seen in the CHARGE syndrome patients, although 3 of 59 (5%) patients with CHARGE syndrome had an Omenn-like syndrome, which has autoimmune-like features. An explanation of the autoimmune predisposition in 22q11.2 deletion syndrome might be a reduced level of natural regulatory T-cells (nTreg).…”

Section: Immunological Abnormalities Reported In Charge Syndromementioning

confidence: 99%

CHARGE syndrome: a review of the immunological aspects

et al. 2015

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CHARGE syndrome is caused by a dominant variant in the CHD7 gene. Multiple organ systems can be affected because of haploinsufficiency of CHD7 during embryonic development. CHARGE syndrome shares many clinical features with the 22q11.2 deletion syndrome. Immunological abnormalities have been described, but are generally given little attention in studies on CHARGE syndrome. However, structured information on immunological abnormalities in CHARGE patients is necessary to develop optimal guidelines for diagnosis, treatment and follow-up in these patients. Here, we provide an overview of the current literature on immunological abnormalities in CHARGE syndrome. We also explore immunological abnormalities in comparable multiple congenital anomaly syndromes to identify common immunological phenotypes and genetic pathways that might regulate the immune system. Finally, we aim to identify gaps in our knowledge on the immunological aspects in CHARGE syndrome that need further study.

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“…8,9 Patients gener-ally exhibit a mild to moderate decrement in T-cell numbers with preservation of T-cell function. 10 Thus, patients with chromosome 22q11.2 deletion syndrome are at risk for disease from attenuated vaccine-strain virus and from wild-type viral infection. The aims of this study were to investigate the incidence of side effects after live viral vaccine administration in a population with chromosome 22q11.2 deletion syndrome.…”

mentioning

confidence: 99%

Safety of Live Viral Vaccines in Patients With Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)

et al. 2003

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Live attenuated viral vaccines are a part of routine childhood immunizations and over the years have proved their safety and efficacy in the general population. Mild adverse effects of measles-mumps-rubella (MMR) vaccination include fever, rash, and lymphadenopathy and occur in approximately 5% to 15% of vaccine recipients. 1,2 Similarly, side effects of the varicella vaccine include injection site reactions, fever, and rash, which occur in 5% to 30% of individuals. [3][4][5] Severe side effects are exceedingly rare with both vaccinations. 5,6 The package inserts for both the varicella and MMR vaccines warn against use in patients with any form of cellular or humoral immunodeficiency. However, the most recent Advisory Committee on Immunization Practices allows the use of varicella vaccine in patients with a humoral immunodeficiency as well as in patients with human immunodeficiency virus with age-specific CD4 count Ն25%. 4 No published guidelines exist for the administration of these vaccines to patients with chromosome 22q11.2 deletion syndrome. 7 This syndrome is associated with thymic hypoplasia and diminished T-cell numbers and has a wide spectrum of phenotypic features that include cardiac anomalies, dysmorphic facial features, and hypocalcemia. 8,9 Patients gener-

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Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome)

Cited by 237 publications

References 51 publications

Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements

Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements

CHARGE syndrome: a review of the immunological aspects

Safety of Live Viral Vaccines in Patients With Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)

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