Byrne J, Carolan S. Adverse reproductive outcomes among pregnancies of aunts and (spouses of) uncles in Irish families with neural tube defects. American journal of medical genetics. Part A. 2006 Jan 1;140(1):52-61.
Boyne Research Institute, 5 Potato Market Square East, Drogheda, Ireland. boyne.research@verizon.net
Adverse pregnancy outcomes may be more frequent among sibs of individuals with neural tube defects (NTDs), and transmission of risk in families with an NTD may be more frequent among maternal relatives. In a study designed to evaluate matrilineal risk for NTDs, we compared adverse pregnancy outcomes among maternal and paternal first cousin pregnancies. Pregnancy histories were obtained by interview with 288 uncles and aunts (parents of the first cousin pregnancies) in 48 Irish NTD families. We analyzed pregnancy outcomes (preterm deliveries, stillbirths, and miscarriages) among 1,033 singleton first cousin pregnancies and compared risk among maternal versus paternal relatives. Maternal first cousin pregnancies were more likely to end adversely when compared to paternal first cousin pregnancies (17.4% vs. 11.7%, P = 0.01). In a logistic regression analysis of pregnancies unaffected by birth defects, maternal line remained independently associated with adverse outcomes (odds ratio (OR) = 1.55, 95% confidence interval (CI) 1.06, 2.27) after controlling for NTD type, maternal age, maternal smoking during pregnancy, first cousin pregnancy's year of birth. The excess risk with maternal line related mainly to spina bifida occulta families (OR = 42.4; CI 2.64, 681; P = 0.008); risk in open spina bifida families was 1.24 (CI 0.82, 1.87; P = 0.3). These results support the hypothesis of excess risk for adverse pregnancy outcomes among maternal relatives in NTD families. Further work is needed, epidemiological as well as clinical and molecular, not only to confirm these findings, but also to define the underlying biological mechanisms linking adverse reproductive outcomes, excess maternal risk and occurrence of NTDs.
PMID: 16333827
Showing posts with label Materal Effect. Show all posts
Showing posts with label Materal Effect. Show all posts
Thursday, April 16, 2009
Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects.
Deak KL, Siegel DG, George TM, Gregory S, Ashley-Koch A, Speer MC; NTD Collaborative Group. (2008) Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects. Birth defects research. Part A, Clinical and molecular teratology. 2008 Oct;82(10):662-9.
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA.
BACKGROUND: Neural tube defects (NTDs), including spina bifida and anencephaly, are the second most common birth defect with an incidence of 1/1000. Genetic factors are believed to contribute to NTD risk and family-based studies can be useful for identifying such risk factors.
METHODS: We ascertained 1066 NTD families (1467 affected patients), including 307 multiplex NTD families. We performed pedigree analysis to describe the inheritance patterns, pregnancy outcomes, and recurrence risks to relatives of various types.
RESULTS: Myelomeningocele or spina bifida (66.9%) and cranial defects (17.7%) were the most common NTD subtypes observed. The overall male:female ratio for affected individuals was 0.82, and there were even fewer males among individuals with an upper level NTD (0.62). Among twins, 2 of the 5 monozygotic twins and only 3 of 35 dizygotic twins were concordant, while 27% of the same sex twins were concordant, but none of the different sex twins. The estimated 6.3% recurrence risk to siblings (CI 0.04-0.08) is consistent with previous reports. Families with two or more affected individuals show a higher proportion of female transmitters (p = 0.0002). Additionally, the number of affected relatives in maternal compared to paternal lineages was more than double (p = 0.006). There were significantly more miscarriages, infant deaths, and stillborn pregnancies of the maternal aunts and uncles (p < 0.0001) and of first cousins (p = 0.04).
CONCLUSIONS: Our data provide several lines of evidence consistent with a maternal effect, as well as a sex-influenced effect, in the etiology of NTDs.
PMID: 18937341
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA.
BACKGROUND: Neural tube defects (NTDs), including spina bifida and anencephaly, are the second most common birth defect with an incidence of 1/1000. Genetic factors are believed to contribute to NTD risk and family-based studies can be useful for identifying such risk factors.
METHODS: We ascertained 1066 NTD families (1467 affected patients), including 307 multiplex NTD families. We performed pedigree analysis to describe the inheritance patterns, pregnancy outcomes, and recurrence risks to relatives of various types.
RESULTS: Myelomeningocele or spina bifida (66.9%) and cranial defects (17.7%) were the most common NTD subtypes observed. The overall male:female ratio for affected individuals was 0.82, and there were even fewer males among individuals with an upper level NTD (0.62). Among twins, 2 of the 5 monozygotic twins and only 3 of 35 dizygotic twins were concordant, while 27% of the same sex twins were concordant, but none of the different sex twins. The estimated 6.3% recurrence risk to siblings (CI 0.04-0.08) is consistent with previous reports. Families with two or more affected individuals show a higher proportion of female transmitters (p = 0.0002). Additionally, the number of affected relatives in maternal compared to paternal lineages was more than double (p = 0.006). There were significantly more miscarriages, infant deaths, and stillborn pregnancies of the maternal aunts and uncles (p < 0.0001) and of first cousins (p = 0.04).
CONCLUSIONS: Our data provide several lines of evidence consistent with a maternal effect, as well as a sex-influenced effect, in the etiology of NTDs.
PMID: 18937341
Subscribe to:
Posts (Atom)
