Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: implications for a survival advantage

Charlotte A Hobbs; Mario A Cleves; Ronald M Lauer; Trudy L Burns; S Jill James

doi:10.1002/ajmg.10704

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Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: implications for a survival advantage

Journal article

Peer reviewed

Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: implications for a survival advantage

Charlotte A Hobbs, Mario A Cleves, Ronald M Lauer, Trudy L Burns and S Jill James

American journal of medical genetics, Vol.113(1), pp.9-14

11/15/2002

DOI: 10.1002/ajmg.10704

PMID: 12400059

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Abstract

We have examined the transmission frequencies of the methylenetetrahydrofolate reductase (MTHFR) 677 T and C alleles from heterozygous parents to children with Down syndrome (trisomy 21) in 202 Caucasian families. Our results indicated that the MTHFR 677T allele was transmitted to children with Down syndrome at a significantly higher rate than would be expected based on Mendelian inheritance patterns, and the C allele was transmitted at a significantly lower rate (P < 0.009). Transmission frequencies were also examined independently for maternally and paternally transmitted alleles to assess potential parent-of-origin effects. Because the vast majority of conceptions with trisomy 21 end in pregnancy loss, we questioned whether the observed preferential transmission of the T allele to this population of liveborn infants with Down syndrome could reflect a survival advantage. A plausible biochemical interpretation of these results is presented based on a maternal-fetal MTHFR 677T allele interaction in the context of the constitutive overexpression of three copies of the cystathionine beta synthase gene in the trisomy 21 fetus. Published 2002 Wiley-Liss, Inc.

Alleles

Arkansas

Down Syndrome - enzymology

Down Syndrome - genetics

European Continental Ancestry Group

Fathers

Female

Genetic Carrier Screening

Genomic Imprinting

Genotype

Humans

Infant

Male

Methylenetetrahydrofolate Reductase (NADPH2)

Mothers

Nuclear Family

Oxidoreductases Acting on CH-NH Group Donors - genetics

Details

Title: Subtitle: Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: implications for a survival advantage
Creators: Charlotte A Hobbs - University of Arkansas for Medical Sciences
Mario A Cleves - Arkansas Children's Hospital
Ronald M Lauer - University of Iowa Hospitals and Clinics
Trudy L Burns - University of Iowa Hospitals and Clinics
S Jill James - National Center for Toxicological Research
Resource Type: Journal article
Publication Details: American journal of medical genetics, Vol.113(1), pp.9-14
DOI: 10.1002/ajmg.10704
PMID: 12400059
ISSN: 0148-7299
eISSN: 1096-8628
Grant note: HL 62178-01 / NHLBI NIH HHS R01 HD24605 / NICHD NIH HHS HD 39054-01 / NICHD NIH HHS
Language: English
Date published: 11/15/2002
Academic Unit: Epidemiology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984363633102771

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