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1.
Mary J. Seller 《American journal of medical genetics. Part A》1995,58(4):332-336
While neural tube defects (NTD) overall have a female sex bias, this does not apply to all sites along the neuraxis. The findings regarding sex and NTD in a series of midtrimester fetuses are reviewed, and then analysed in terms of the recent hypothesis that during embryogenesis of the human neural tube there are multiple closure sites, rather than a single zipping up process. Females more often than males tend to have craniorachischisis, spina bifida involving the thorax, the holoacrania form of anencephaly, anencephaly and cervical spina bifida and encephalocoeles, while males more often than females have spina bifida affecting the lower spine. Meroacrania occurs equally in both sexes. Other sources indicate that there is a male bias in frontoethmoidal encephalocoeles. Since sex seems to be a factor that is differentially associated with lack of closure of specific areas of the neural tube, it would seem to support the notion that there are multiple closure sites in the human neural tube. However, no association was found between a particular sex and either the type of NTD which have an isolated abnormality or those NTD associated with developmental abnormalities of other body systems. © 1995 Wiley-Liss, Inc. 相似文献
2.
Zhu H Yang W Lu W Zhang J Shaw GM Lammer EJ Finnell RH 《Molecular genetics and metabolism》2006,87(1):66-70
Folate binding protein 1 (Folr1) knockout mice with low maternal folate concentrations have been shown to be excellent animal models for human folate-responsive neural tube defects (NTDs). Previous studies using the Folr1 knockout mice revealed that maternal folate supplementation up-regulates the expression of the PCMT1 gene in Folr1 nullizygous neural tube tissue during neural tube closure. PCMT1 encodes the protein repair enzyme l-isoaspartate (d-aspartate) O-methyltransferase (PIMT) that converts abnormal d-aspartyl and l-isoaspartyl residues to the normal l-aspartyl form. PIMT is known to protect certain neural cells from Bax-induced apoptosis. Pcmt1-deficient mice present with abnormal AdoMet/AdoHcy homeostasis. We hypothesized that a known functional polymorphism (Ile120Val) in the human PCMT1 gene is associated with an increased risk of folate-responsive human NTDs. A case-control study was conducted to investigate a possible association between this polymorphism and risk of spina bifida. Compared to the Ile/Ile and Ile/Val genotypes, the homozygous Val/Val genotype showed decreased risk for spina bifida (adjusted odds ratio=0.6, 95% confidence interval: 0.4-0.9). Our results showed that the Ile120Val polymorphism of PCMT1 gene is a genetic modifier for the risk of spina bifida. Val/Val genotype was associated with a reduction in risk for spina bifida. 相似文献
3.
It is suggested that the major genetic factor in determining the birth of children with neural tube defects may be a single X-linked gene. It acts as an X-linked dominant, not by producing neural tube defects, but by enabling the affected fetus to survive selective spontaneous abortion. This mechanism, mediated at the deciduoplacental junction, may be under the control of both maternal and fetal genes. With more mutant alleles, survival would become more likely, reaching a maximum in the homozygous affected female fetus of a homozygous affected mother. The female excess in anancephaly is greater than that in spina bifida because of its prenatal severity, thus requiring relatively more mutant alleles for survival. 相似文献
4.
Does lumbosacral spina bifida arise by failure of neural folding or by defective canalisation? 总被引:2,自引:0,他引:2
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The aim of this study was to determine whether open lumbosacral spina bifida results from an abnormality of neural folding (primary neurulation) or medullary cord canalisation (secondary neurulation). Homozygous curly tail (ct) mouse embryos were studied as a model system for human neural tube defects. The rostral end of the spina bifida was found to lie at the level of somites 27 to 32 in over 90% of affected ct/ct embryos. Indian ink marking experiments using non-mutant embryos showed that the posterior neuropore closes, and primary neurulation is completed, at the level of somites 32 to 34. Since neurulation in mammals progresses in a craniocaudal sequence, without overlap between regions of primary and secondary neurulation, we conclude that spina bifida in ct/ct embryos arises initially as a defect of primary neurulation. The position of posterior neuropore closure in human embryos is estimated to lie at the level of the future second sacral segment indicating that in humans, as in the ct mouse, lumbosacral spina bifida usually arises as a defect of posterior neuropore closure. Cranial NTD affect females predominantly, whereas lower spinal NTD are more common in males, both in humans and ct mice. We offer an explanation for this phenomenon based on (a) differences in the effect of embryonic growth retardation on the likelihood that an embryo will develop either cranial or lower spinal NTD and (b) differences in the rate of growth and development of male and female embryos at the time of neurulation. 相似文献
5.
It has been suggested that neural tube defects (NTDs) of the upper type (anencephaly, encephalocele, and thoracic spina bifida) may have a pathogenesis different from those of the lower type (lumbosacral spina bifida), since recurrent cases within a sibship were said always to be concordant with respect to NTD type. Also, spontaneous abortion, additional malformation, and recurrence rate were observed to be higher in the upper group, and there was an excess of females in upper NTD probands. To test this hypothesis, we measured the above variables in upper and lower NTDs in a sample from Quebec. We found less than full concordance (50%) of NTD type in 18 sib pairs. Recurrence rate was not significantly lower in the lower NTD group (5.6 v 5.8%). The other variables were in general agreement with previous studies, inconsistent findings possibly attributable to different NTD population incidences. These findings can be accounted for if upper and lower NTDs share a similar pathogenesis and the embryo is more susceptible during early than late neural tube formation. 相似文献
6.
Julianne Byrne Armando Cama Marie Reilly Mariantonietta Vigliarolo Laura Levato Luca Boni Natale Lavia Luciano Andreussi 《American journal of medical genetics. Part A》1996,66(3):303-310
Periconceptional vitamin supplementation with folate prevents about three-quarters of expected cases of neural tube defects (NTDs) in clinical trials. However, vitamin action may be regulated at the level of the gene, and individual susceptibility to environmental agents, including dietary components, also may be under genetic control. We investigated the presence of familial factors in a retrospective case control study of neural tube defects in Genoa, Italy. Cases included all patients treated at a single pediatric neurosurgical service. Controls matched on age and sex came from the same hospital. We found strong evidence for the contribution of genetic factors in this study. There was an excess risk of 14 for the occurrence of NTDs in first-degree relatives compared to controls (P < .0005). There was no difference in sex ratio in any group of relatives, but maternal grandparents of children with a high spinal lesion had 14% fewer offspring than paternal grandparents (P < .005), possibly because of excess miscarriages. Our study is the first to show complex patterns of inheritance in spina bifida families affecting three generations in one clinical subgroup and preferentially on the mother's side. These results support a role for genomic imprinting and highlight the value of multidisciplinary epidemiologic and clinical studies that include multiple generations. New studies incorporating dietary and genetic approaches will help clarify and extend these findings. © 1996 Wiley-Liss, Inc. 相似文献
7.
W H James 《Journal of medical genetics》1979,16(5):384-388
Published reports on the sex ratio of spina bifida have been reviewed. With one exception, there seems to be no evidence of variation in the sex ratio of spina bifida. In particular, unlike anencephaly, the sex ratio of spina bifida seems to be unrelated to the prevalence of the malformation: this (M/(M+F)) is of the order of 0.44 in respect of all spina bifida births (liveborn and stillborn). The sex ratio of spina bifida in Negroes does not seem to differ from that in whites (though the data on this point are not numerous). The exception noted above concerns spina bifida occurrring in twins: these cases are disproportionately often female. The point stands in need of explanation. 相似文献
8.
Joël Zlotogora 《American journal of medical genetics. Part A》1995,56(1):87-89
Anencephaly is relatively frequent in Jews originating from Iran, in particular when its incidence is compared to that of open spina bifida in the same population (12 cases of anencephaly out of 14 cases of neural tube defects). The high incidence of this disorder in Iranian Jews, a relatively isolated community with a very high rate of consanguinity, suggests that anencephaly is caused by a major recessive gene. This possibility is supported by the sex ratio among these patients, which was significantly different from that observed for patients with anencephaly in other populations. © 1995 Wiley-Liss, Inc. 相似文献
9.
Wong RL Wlodarczyk BJ Min KS Scott ML Kartiko S Yu W Merriweather MY Vogel P Zambrowicz BP Finnell RH 《Human molecular genetics》2008,17(4):587-601
Neural tube defects (NTDs) are birth defects that can be disabling or lethal and are second in their prevalence after cardiac defects among major human congenital malformations. Spina bifida is a NTD where the spinal cord is dysplastic, and the overlying spinal column is absent. At present, the molecular mechanisms underlying the spinal bifida development are largely unknown. In this study, we present a Fkbp8 mouse mutant that has an isolated and completely penetrant spina bifida, which is folate- and inositol-resistant. Fkbp8 mutants are not embryo lethal, but they display striking features of human spina bifida, including a dysplastic spinal cord, open neural canal and disability. The loss of Fkbp8 leads to increased apoptosis in the posterior neural tube, demonstrating that in vivo FKBP8 inhibits cell death. Gene expression analysis of Fkbp8 mutants revealed a perturbation of expression of neural tube patterning genes, suggesting that endogenous FKBP8 activity establishes dorso-ventral patterning of the neural tube. These studies demonstrate that Fkbp8 is not important for embryo survival, but is essential for spinal neural tube patterning, and to block apoptosis, in the developing neural tube. The mutant Fkbp8 allele is a new experimental model which will be useful in dissecting the pathogenesis of spinal NTDs, and enhance our understanding of the etiology of human NTDs. 相似文献
10.
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. 相似文献
11.
J I Rodríguez M García C Morales A Morillo A Delicado 《American journal of medical genetics》1990,36(4):513-516
Abnormalities of the CNS, such as arhinencephaly or holoprosencephaly, are common findings in trisomy 13 syndrome. However, neural tube defects (NTDs) are rarely reported. A review of 267 patients in the literature on reported CNS developmental defects in trisomy 13 syndrome showed only 6 patients with lumbosacral NTDs. No case of encephalocele or anencephaly was found. We report on 3 patients with spina bifida from the records of 34 necropsies of karyotyped trisomy 13 syndrome, which were found among 403,710 births. 相似文献
12.
A family showing apparent X linked inheritance of both anencephaly and spina bifida. 总被引:3,自引:1,他引:3
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O Jensson A Arnason H Gunnarsdottir I Petursdottir R Fossdal S Hreidarsson 《Journal of medical genetics》1988,25(4):227-229
A family is reported which includes five males, two with spina bifida, two sibs with anencephaly, and one with both high and low spinal lesions. The affected subjects came from four sibships in three generations. The mode of inheritance of these neural tube defects is consistent with X linkage. 相似文献
13.
Zhu H Curry S Wen S Wicker NJ Shaw GM Lammer EJ Yang W Jafarov T Finnell RH 《American journal of medical genetics. Part A》2005,135(3):274-277
Abnormalities in folate and/or homocysteine metabolism may adversely influence embryonic development, leading to the birth of infants with a variety of congenital malformations, including neural tube defects (NTDs) and craniofacial abnormalities. Based upon suggestive evidence that periconceptional folic acid supplementation is effective in preventing a significant proportion of the aforementioned birth defects, genetic variation in the folate biosynthetic pathways may influence the infant's susceptibility to these birth defects. The goal of our study was to investigate sequence variations in the betaine-homocysteine methyltransferase (BHMT) and betaine-homocysteine methyltransferase (BHMT2) genes as modifiers of risk of spina bifida, cleft palate, and cleft lip and palate. The results of this study indicated that individuals homozygous for the single nucleotide polymorphism R239Q in BHMT did not have elevated risks for spina bifida. Genotype frequencies for the BHMT2 rs626105 polymorphism also did not reveal any elevated risks for spina bifida, and only a modest, imprecise elevation of risk for orofacial clefts. The results of these experiments suggest that variants of the BHMT/BHMT2 genes in infants do not substantially contribute to the risk of spina bifida or orofacial clefts in our study population. 相似文献
14.
N. M. J. van der Put L. P. van den Heuvel R. P. M. Steegers-Theunissen F. J. M. Trijbels T. K. A. B. Eskes E. C. M. Mariman M. den Heyer H. J. Blom 《Journal of molecular medicine (Berlin, Germany)》1996,74(11):691-694
Periconceptional folate intake reduces both the occurrence and recurrence risk of neural tube defects. Plasma homocysteine
levels can be elevated in mothers of a child with a neural tube defect, suggesting a dysfunctional folate metabolism. Very
recently we showed that a common 677C→T mutation in the 5,10-methylene tetrahydrofolate reductase gene, causing thermolability
of the enzyme, is a risk factor for spina bifida offspring. Restriction enzyme analysis of the genomic 5,10-methylene tetrahydrofolate
reductase polymerase chain reaction fragment revealed a significantly higher prevalence of a +/+ genotype among spina bifida
patients and their mothers. The risk for spina bifida offspring is the strongest if both the mother and her child have the
mutation in the homozygous state. Enzymatic analysis showed that homozygosity for the 677C→T mutation causes a decreased 5,10-methylene
tetrahydrofolate reductase activity, resulting in elevated plasma homocysteine and red blood cell folate levels and lowered
plasma folate and cysteine values. This extended study demonstrates that a nucleotide substitution in the coding region of
5,10-methylene tetrahydrofolate reductase, resulting in reduced activity and an impaired homocysteine and folate metabolism,
is a genetic risk factor for spina bifida.
Received: 24 May 1996 / Accepted: 14 August 1996 相似文献
15.
Levels of alpha-fetoprotein in amniotic fluids of mice (curly-tail) with neural tube defects. 总被引:1,自引:0,他引:1
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Mutant curly-tail mice are genetically predisposed to produce offspring with neural tube defects. Estimation of alpha-fetoprotein in the amniotic fluid of fetuses of these mutants has shown that the levels are raised in fetuses with exencephaly and open spina bifida. This suggests that these mice are a valid model for studies of the aetiology and genesis of neural tube defects in man. 相似文献
16.
Transcervical embryoscopy, a new technique for direct visualization of the first trimester conceptus was carried out in 116 cases of missed abortion. Embryonic neural tube defects and other localized developmental defects, were diagnosed in 10 out of 99 cases in which a complete embryoscopic evaluation was possible. All eight successfully karyotyped cases had a numerical chromosomal abnormality. A ninth unkaryotyped embryo with open spina bifida showed, on embryoscopy, a malformation pattern highly suggestive of triploidy. Our embryoscopic and cytogenetic findings provide valuable information for genetic counseling in future pregnancies. 相似文献
17.
Although most neural tube defects (anencephaly, spina bifida) occur as isolated malformations, a substantial proportion are attributable to chromosome anomalies, known teratogens, or component manifestations of multiple anomaly syndromes. This review describes known chromosome alterations and the candidate genes residing in the altered region, as well as syndromes associated with neural tube defects and causative genes, if known. 相似文献
18.
Lisi A Botto LD Rittler M Castilla E Bianca S Bianchi F Botting B De Walle H Erickson JD Gatt M De Vigan C Irgens L Johnson W Lancaster P Merlob P Mutchinick OM Ritvanen A Robert E Scarano G Stoll C Mastroiacovo P 《American journal of medical genetics. Part A》2005,(1):49-57
The study evaluated the sex distribution of major isolated malformations and common trisomies among a large and geographically varied sample. Eighteen registries from 24 countries contributed cases, which were centrally reviewed and classified in three clinical types as isolated, associated, or syndromic. We selected cases of 26 major defects (n = 108,534); trisomy 21, 18, and 13 (n = 30,114); other syndromes (n = 2,898); and multiple congenital anomalies (n = 24,197), for a total of 165,743 cases. We observed a significant deviation of sex distribution (compared to a sex ratio of 1.06 or male proportion of 51.4%) for 24 of the 29 groups (a male excess in 16, a female excess in 8), and in 8 of such groups these estimates varied significantly across registries. A male excess was noted for two left obstructive cardiac defects (hypoplastic left heart and coarctation of the aorta) and a female excess for all the main types of neural tube defects. A male excess was seen for omphalocele but not gastroschisis. For neural tube defects the female excess tended to be stronger in areas with historically high prevalence for these defects. For 15 of the 26 birth defects the sex distribution differed among isolated, associated, and syndromic cases. Some of these epidemiologic commonalities are consistent with known or putative developmental processes. Further, the geographic variation for some defects may reflect local prevalence rates and risk factors. Finally, the findings underscore the need for clinical classification (e.g., into isolated, multiple, syndromes) in studies of birth defects. 相似文献
19.
Transcervical embryoscopy, a new technique for direct visualization of the first trimester conceptus was carried out in 116 cases of missed abortion. Embryonic neural tube defects and other localized developmental defects, were diagnosed in 10 out of 99 cases in which a complete embryoscopic evaluation was possible. All eight successfully karyotyped cases had a numerical chromosomal abnormality. A ninth unkaryotyped embryo with open spina bifida showed, on embryoscopy, a malformation pattern highly suggestive of triploidy. Our embryoscopic and cytogenetic findings provide valuable information for genetic counseling in future pregnancies. © 2001 Wiley‐Liss, Inc. 相似文献