Possible association of sudden infant death with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes

Schneider, P. M.; Wendler, Christine; Riepert, T.; Braun, Liane; Schacker, U.; Horn, Michael; Althoff, H; Mattern, Rainer; Rittner, Christian

doi:10.1007/bf01958273

Cited by 38 publications

(22 citation statements)

References 32 publications

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“…The first SIDS candidate genes that were investigated in relation to the immune system response to infection were in the major histocompatibility complex (HLA in humans, chromosome 6p). HLA-DR2 was decreased in 39 SIDS cases versus controls [Keller et al, 1990], but this relationship was not confirmed in two other studies (40 SIDS cases, Schneider et al, 1989;39 SIDS cases, Kaada and Spurkland, 1992). The C4 gene (also involved in the immune system and in linkage disequilibrium with HLA) [O'Neill et al, 1978] has also been investigated with SIDS.…”

Section: Infection/inflammation Genes In Sidsmentioning

confidence: 94%

“…There are two isotypes of C4, C4A and C4B; C4A preferentially reacts with amino groups to form amide bonds and C4B preferentially binds hydroxyl groups to form ester bonds [Law et al, 1984]. Schneider et al [1989;40 SIDS cases], Keller et al [1990;39 SIDS cases], and Opdal et al [1994;61 SIDS cases] found increases in C4B deletions in SIDS cases versus controls that were not statistically significant overall, but in the Schneider et al [1989] and Opdal et al [1994] studies the increases were significant in subsets of cases that had evidence of recurrent infections [Schneider et al, 1989] (P ¼ 0.01 for C4B deletions) or signs of infection prior to death [Opdal et al, 1994] (P ¼ 0.03 for C4A and C4B deletions). Opdal et al [1999b] then investigated C4 in 104 SID cases (89 totally unexplained SIDS plus 15 borderline SID), 52 with and 52 without slight infections prior to death; and 84 living infants, 22 with and 62 without infection.…”

Section: Infection/inflammation Genes In Sidsmentioning

confidence: 99%

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Sudden Infant Death Syndrome: Review of implicated genetic factors

Weese‐Mayer

Ackerman

Marazita

et al. 2007

American J of Med Genetics Pt A

123

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Genetic studies in Sudden Infant Death Syndrome (SIDS) have been motivated by clinical, epidemiological, and/or neuropathological observations in SIDS victims, with subsequent pursuit of candidate genes in five categories: (1) genes for ion channel proteins based on electrocardiographic evidence of prolonged QT intervals in SIDS victims, (2) gene for serotonin transporter based on decreased serotonergic receptor binding in brainstems of SIDS victims, (3) genes pertinent to the early embryology of the autonomic nervous system (ANS) (and with a link to the 5-HT system) based on reports of ANS dysregulation in SIDS victims, (4) genes for nicotine metabolizing enzymes based on evidence of cigarette smoking as a modifiable risk factor for SIDS, and (5) genes regulating inflammation, energy production, hypoglycemia, and thermal regulation based on reports of postnatal infection, low birth weight, and/or overheating in SIDS victims. Evidence for each of these classes of candidate genes is reviewed in detail. As this review indicates, a number of genetically controlled pathways appear to be involved in at least some cases of SIDS. Given the diversity of results to date, genetic studies support the clinical impression that SIDS is heterogeneous with more than one entity and with more than one possible genetic etiology. Future studies should consider expanded phenotypic features that might help clarify the heterogeneity and improve the predictive value of the identified genetic factors. Such features should be evaluated to the extent possible in both SIDS victims and their family members. With 2,162 infants dying from SIDS in 2003 in the U.S. alone, and improved but still imperfect parent and caretaker compliance with known modifiable risk factors for SIDS, it behooves clinicians, researchers, and parents to combine efforts to reach a common goal. The message of the "Back to Sleep" campaign needs to be re-introduced/re-engineered to reach families and caretakers of all ethnic groups. Clinicians and researchers need to gently inform new SIDS parents about the opportunity to contribute tissue to the NICHD-funded University of Maryland Brain and Tissue Bank. By expanding the network of clinicians, scientists, and families working together, and by combined efforts in a collaborative multi-center study of candidate genes and/or genomics, the discovery of the genetic profile of the infant at risk for SIDS can ultimately be determined.

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Section: Infection/inflammation Genes In Sidsmentioning

confidence: 94%

Section: Infection/inflammation Genes In Sidsmentioning

confidence: 99%

Sudden Infant Death Syndrome: Review of implicated genetic factors

Weese‐Mayer

Ackerman

Marazita

et al. 2007

American J of Med Genetics Pt A

123

View full text Add to dashboard Cite

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“…Partial deletions of the complement factor 4 (C4) gene in combination with slight upper airway infections have been related to an increased risk for SIDS [152][153][154] .…”

Section: Predisposing Factorsmentioning

confidence: 99%

Detection rate of Helicobacter pylori stool antigen in newborn infants and small children

Stray-Pedersen

Gaustad

Stray‐Pedersen

et al. 2007

Journal of Perinatal Medicine

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“…32 The C4 gene was investigated among both German and Norwegian SIDS victims (40 and 104 cases, respectively), but neither of the studies detected any differences between SIDS cases and control cases with respect to gene frequencies. 33,34 However, both studies revealed an association between slight infections before death and partial deletions of either the C4A or C4B gene, which may indicate that this combination indicates increased risk of sudden infant death.…”

Section: C4mentioning

confidence: 96%

The Sudden Infant Death Syndrome Gene: Does It Exist?

2004

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ABSTRACT. Background. Sudden infant death syndrome (SIDS) is in a difficult position between the legal and medical systems. In the United Kingdom, prosecutors have for years applied the simple rule that 1 unexpected death in a family is a tragedy, 2 are suspicious, and 3 are murder. However, it seems that the pendulum has now swung to the opposite extreme; mutations or polymorphisms with unclear biological significance are accepted in court as possible causes of death. This development makes research on genetic predisposing factors for SIDS increasingly important, from the standpoint of the legal protection of infants. The genetic component of sudden infant death can be divided into 2 categories, ie (1) mutations that give rise to genetic disorders that constitute the cause of death by themselves and (2) polymorphisms that might predispose infants to death in critical situations. Distinguishing between these 2 categories is essential, and cases in which a mutation causing a lethal genetic disorder is identified should be diagnosed not as SIDS but as explained death.Genetic Alterations That May Cause Sudden Infant Death. Deficiencies in fatty acid metabolism have been extensively studied in cases of SIDS, and by far the most well-investigated mutation is the A985G mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene, which is the most prevalent mutation causing MCAD deficiency. However, <1% of sudden infant death cases investigated have this mutation, and findings of biochemical profiles seen in specific fatty acid oxidation disorders in a number of such cases emphasize the importance of investigating fatty acid oxidation disorders other than MCAD deficiency. Severe acute hypoglycemia may cause sudden death among infants, but only rare novel polymorphisms have been found when key proteins involved in the regulation of blood glucose levels are investigated in cases of SIDS. The long QT syndrome (LQTS) is another inherited condition proposed as the cause of death in some cases of sudden infant death. The LQTS is caused by mutations in genes encoding cardiac ion channels, and mutations in the genes KVLQT1 and SCNA5 have been identified in cases initially diagnosed as SIDS, in addition to several polymorphisms in these 2 genes and in the HERG gene. In addition, genetic risk factors for thrombosis were investigated in a small number of SIDS cases; the study concluded that venous thrombosis is not a major cause of sudden infant death. Conclusions. All mutations giving rise to metabolic disorders known to be associated with life-threatening events are possible candidates for genes involved in cases of sudden infant death, either as a cause of death or as a predisposing factor. It is necessary to distinguish between lethal mutations leading to diseases such as MCAD and LQTS, and polymorphisms (for instance, in the IL-10 gene and mtDNA) that are normal gene variants but might be suboptimal in critical situations and thus predispose infants to sudden infant death. It is unlikely that one mutation or polymorphism...

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Possible association of sudden infant death with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes

Cited by 38 publications

References 32 publications

Sudden Infant Death Syndrome: Review of implicated genetic factors

Sudden Infant Death Syndrome: Review of implicated genetic factors

Detection rate of Helicobacter pylori stool antigen in newborn infants and small children

The Sudden Infant Death Syndrome Gene: Does It Exist?

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