Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects.
Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects.
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DOI：
10.1002/bdra.20511
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发表时间：
2008-10
影响因子：
--
通讯作者：
Speer, Marcy C.
中科院分区：
文献类型：
--
作者：
Deak, Kristen L.;Siegel, Deborah G.;George, Timothy M.;Gregory, Simon;Ashley-Koch, Allison;Speer, Marcy C.
神经管缺陷(NTDS)，包括脊柱裂和无脑畸形，是第二常见的出生缺陷，发病率为1/1000。遗传因素被认为是导致NTD风险的因素，基于家庭的研究有助于识别此类风险因素。我们确定了1066个NTD家系(1467名患者)，其中包括307个多基因NTD家系。我们进行了家系分析，以描述遗传模式、妊娠结局和不同类型亲属的复发风险。脊髓脊膜膨出或脊柱裂(66.9%)和颅骨缺陷(17.7%)是最常见的NTD亚型。受影响个体的总体男性：女性比率为0.82，NTD水平较高的个体中男性更少(0.62)。在双胞胎中，五个同卵双胞胎中有两个是一致的，35个异卵双胞胎中只有三个是一致的，而27%的同性双胞胎是一致的，但不同性别的双胞胎中没有一个。估计的6.3%的兄弟姐妹复发风险(CI 0.04 0.08)与以前的报告一致。有两个或两个以上感染者的家庭女性传播者比例较高(P=0.0002)。此外，与父系相比，母系中受影响的亲属数量增加了一倍多(P=0.006)。母亲的阿姨和叔叔(P=0.0001.0 1)和近亲(P=0.0 4)的流产、婴儿死亡和死胎的发生率显著高于母亲(P=0.0 4)。我们的数据提供了与NTDS病因学中的母体效应以及性别影响效应相一致的几条证据。
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. 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. 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, two of the five monozygotic twins and only three 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 in the maternal aunts and uncles (P = < 0.0001) and of first cousins (P = 0.04). Our data provide several lines of evidence consistent with a maternal effect, as well as a sex-influenced effect, in the etiology of NTDs.
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影响因子：
4
作者：
CARTER, CO;EVANS, K
通讯作者：
EVANS, K
DOI：
10.1002/ajmg.1320110305
发表时间：
1982-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
DEMENAIS, F;LEMERRER, M;ELSTON, RC
通讯作者：
ELSTON, RC
DOI：
10.1002/ajmg.1320260325
发表时间：
1987-03-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
SELLER, MJ
通讯作者：
SELLER, MJ
DOI：
10.1002/ajmg.1320440426
发表时间：
1992-11-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
CHATKUPT, S;LUCEK, PR;JOHNSON, WG
通讯作者：
JOHNSON, WG
影响因子：
4
作者：
MARIMAN, ECM;HAMEL, BCJ
通讯作者：
HAMEL, BCJ