Abstract
We have previously identified polymorphisms in the serotonin transporter gene promoter region and in intron 2 that were more common among sudden infant death syndrome (SIDS) cases compared with control subjects. To elucidate further the genetic profile that might increase an infant's vulnerability to SIDS, we focused on the recognized relationship between autonomic nervous system (ANS) dysregulation and SIDS. We therefore studied genes pertinent to early embryologic development of the ANS, including MASH1, BMP2, PHOX2a, PHOX2b, RET, ECE1, EDN1, TLX3, and EN1 in 92 probands with SIDS and 92 gender- and ethnicity-matched control subjects. Eleven protein-changing rare mutations were identified in 14 of 92 SIDS cases among the PHOX2a, RET, ECE1, TLX3, and EN1 genes. Only 1 of these mutations (TLX3) was identified in 2 of 92 control subjects. Black infants accounted for 10 of these mutations in SIDS cases and 2 control subjects. Four protein-changing common polymorphisms were identified in BMP2, RET, ECE1, and EDN1, but the allele frequency did not differ between SIDS cases and control subjects. However, among SIDS cases, the allele frequency for the BMP2 common polymorphism demonstrated ethnic differences; among control subjects, the allele frequency for the BMP2 and the ECE1 common polymorphisms also demonstrated ethnic differences. These data represent further refinement of the genetic profile that might place an infant at risk for SIDS.
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Abbreviations
- SIDS:
-
sudden infant death syndrome
- 5HTT:
-
serotonin transporter gene
- ANS:
-
autonomic nervous system
- CCHS:
-
congenital central hypoventilation syndrome
- BMP2:
-
bone morphogenic protein-2 gene
- MASH1:
-
mammalian achaete-scute homolog-1 gene
- PHOX:
-
paired-like homeobox gene
- RET:
-
rearranged during transfection factor
- ECE1:
-
endothelin converting enzyme-1 gene
- EDN1:
-
endothelin-1 gene
- TLX3:
-
T-cell leukemia homeobox gene
- EN1:
-
engrailed-1 gene
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Acknowledgements
We thank Foster Lewin for the preparation of the DNA; Chinton Desai and Ronak Lahkia, who assisted with PCR assays; Amy Drendel, M.D., and Mary Hayes, M.S.N., for recruitment efforts; and the SIDS cases and their parents, as well as the control subjects who graciously shared their DNA.
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Supported by The CJ Foundation for SIDS, the Joseph Tyler Gertler SIDS Research Fund, The Justin Carl Suth SIDS Research Fund, and the Spastic Paralysis and Allied Diseases of the Central Nervous System Research Foundation of the Illinois-Eastern Iowa District Kiwanis International.
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Weese-Mayer, D., Berry-Kravis, E., Zhou, L. et al. Sudden Infant Death Syndrome: Case-Control Frequency Differences at Genes Pertinent to Early Autonomic Nervous System Embryologic Development. Pediatr Res 56, 391–395 (2004). https://doi.org/10.1203/01.PDR.0000136285.91048.4A
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DOI: https://doi.org/10.1203/01.PDR.0000136285.91048.4A
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