Sudden infant death syndrome: rare mutation in the serotonin system FEV gene.
Recent studies have identified abnormalities in the development and function of medullary serotonin (5-HT) pathways in postmortem brain from sudden infant death syndrome (SIDS) cases, suggesting 5-HT-mediated dysregulation of the autonomic nervous system (ANS) in SIDS. The human fifth Ewing variant (FEV) gene is specifically expressed in central 5-HT neurons in the brain, with a predicted role in specification and maintenance of serotonergic neuronal phenotype. We hypothesized that variations of FEV may underlie abnormalities of the 5-HT system in SIDS cases and thus may be associated with SIDS risk. To elucidate the relationship between variation in FEV and SIDS, DNA was prepared from 96 African American and Caucasian SIDS cases and 96 gender- and ethnicity-matched controls. Standard sequencing and analysis of FEV revealed a heterozygous insertion mutation (IVS-191_190insA) upstream of the 5' exon 3 splice site occurring more frequently in SIDS cases (6/96) compared with controls (0/96; p = 0.01) and in the overall African American group (6/98) compared with the Caucasian group (0/94; p = 0.03). Identification of a variation in a gene responsible for 5-HT neuronal development, exclusively in a subset of African American SIDS cases in this cohort, may help explain both the observed abnormalities of this system in some SIDS cases and the ethnic disparity observed in SIDS.
Rand
Casey M
CM
Department of Pediatrics, Rush Children's Hospital at Rush University Medical Center, Chicago, Illinois 60612, USA.
Berry-Kravis
Elizabeth M
EM
Zhou
Lili
L
Fan
Wenqing
W
Weese-Mayer
Debra E
DE
D001741:Black or African American / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012701:Serotonin / Q000378:metabolism*; D013398:Sudden Infant Death / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors; D044465:White People / Q000235:genetics*
D004268:DNA-Binding Proteins; C474280:FEV protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D012701:Serotonin