Dataset Information

Non-polyalanine repeat mutation in PHOX2B is detected in autopsy cases of sudden unexpected infant death.

ABSTRACT:

Background

Congenital central hypoventilation syndrome (CCHS), which is caused by PHOX2B with phenotypic variations, has a point of controversy: CCHS is putatively involved in autopsy cases of sudden unexpected infant death (SUID) including sudden infant death syndrome.

Objective

The relation of CCHS to SUID cases was investigated by extensive genotyping of PHOX2B.

Methods

We analyzed 93 DNA samples of less than one-year-old SUID cases that were autopsied in our department. Unrelated adult volunteers (n = 942) were used as the control.

Results

No polyalanine tract expansion was detected in the SUID cases. The allelic frequencies of repeat contractions and SNP (rs28647582) in intron 2 were not significantly different from that in those control group. Further extensive sequencing revealed a non-polyalanine repeat mutation (NPARM) of c.905A>C in a sudden death case of a one-month-old male infant. This missense mutation (p.Asn302Thr), registered as rs779068107, was annotated to 'Affected status is unknown', but it might be associated with the sudden death.

Conclusion

NPARM was more plausibly related to sudden unexpected death than expansions because of severe clinical complications. This finding indicates possible CCHS involvement in forensic autopsy cases without ante-mortem diagnosis.

SUBMITTER: Ueda A

PROVIDER: S-EPMC9053812 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Non-polyalanine repeat mutation in PHOX2B is detected in autopsy cases of sudden unexpected infant death.

Ueda Atsushi A Osawa Motoki M Naito Haruaki H Ochiai Eriko E Kakimoto Yu Y

PloS one 20220429 4

<h4>Background</h4>Congenital central hypoventilation syndrome (CCHS), which is caused by PHOX2B with phenotypic variations, has a point of controversy: CCHS is putatively involved in autopsy cases of sudden unexpected infant death (SUID) including sudden infant death syndrome.<h4>Objective</h4>The relation of CCHS to SUID cases was investigated by extensive genotyping of PHOX2B.<h4>Methods</h4>We analyzed 93 DNA samples of less than one-year-old SUID cases that were autopsied in our department. ...[more]

PMID: 35486589

Similar Datasets

Project description:ImportanceRates of maternal obesity are increasing in the US. Although obesity is a well-documented risk factor for numerous poor pregnancy outcomes, it is not currently a recognized risk factor for sudden unexpected infant death (SUID).ObjectiveTo determine whether maternal obesity is a risk factor for SUID and the proportion of SUID cases attributable to maternal obesity.Design, setting, and participantsThis was a US nationwide cohort study using Centers for Disease Control and Prevention National Center for Health Statistics linked birth-infant death records for birth cohorts in 2015 through 2019. All US live births for the study years occurring at 28 weeks' gestation or later from complete reporting areas were eligible; SUID cases were deaths occurring at 7 to 364 days after birth with International Statistical Classification of Diseases, Tenth Revision cause of death code R95 (sudden infant death syndrome), R99 (ill-defined and unknown causes), or W75 (accidental suffocation and strangulation in bed). Data were analyzed from October 1 through November 15, 2023.ExposureMaternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared).Main outcome and measureSUID.ResultsOf 18 857 694 live births eligible for analysis (median [IQR] age: maternal, 29 [9] years; paternal, 31 [9] years; gestational, 39 [2] weeks), 16 545 died of SUID (SUID rate, 0.88/1000 live births). After confounder adjustment, compared with mothers with normal BMI (BMI 18.5-24.9), infants born to mothers with obesity had a higher SUID risk that increased with increasing obesity severity. Infants of mothers with class I obesity (BMI 30.0-34.9) were at increased SUID risk (adjusted odds ratio [aOR], 1.10; 95% CI, 1.05-1.16); with class II obesity (BMI 35.0-39.9), a higher risk (aOR, 1.20; 95% CI, 1.13-1.27); and class III obesity (BMI ≥40.0), an even higher risk (aOR, 1.39; 95% CI, 1.31-1.47). A generalized additive model showed that increased BMI was monotonically associated with increased SUID risk, with an acceleration of risk for BMIs greater than approximately 25 to 30. Approximately 5.4% of SUID cases were attributable to maternal obesity.Conclusions and relevanceThe findings suggest that infants born to mothers with obesity are at increased risk of SUID, with a dose-dependent association between increasing maternal BMI and SUID risk. Maternal obesity should be added to the list of known risk factors for SUID. With maternal obesity rates increasing, research should identify potential causal mechanisms for this association.

Dataset Information

Non-polyalanine repeat mutation in PHOX2B is detected in autopsy cases of sudden unexpected infant death.

Background

Objective

Methods

Results

Conclusion

Publications

Non-polyalanine repeat mutation in PHOX2B is detected in autopsy cases of sudden unexpected infant death.

Similar Datasets

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