Neural tube defects (NTD) are a common birth defect, with both genetic and environmental contributions to their etiology. In mouse, null mutations in Noggin result in fully-penetrant NTDs. We ...investigated Noggin for mutations that may predispose to human NTDs in 202 NTD cases. One variant allele was identified in a male patient with myelomeningocele. The patient's father and a sibling also carried the variant allele, but neither was affected with an open NTD. DNA sequencing confirmed a C1064A missense mutation predicted to result in the conversion of residue 84 from proline to histidine. The variant found in the NTD patient is a newly identified variant, the role of which is uncertain.
Chiari type I malformation has traditionally been defined as a downward herniation of the cerebellar tonsils of ≥5 mm through the foramen magnum and it is likely associated with a volumetrically ...reduced posterior fossa. Syringomyelia is commonly associated with Chiari type I malformation. We estimate the prevalence of these two conditions and determine that they are more common than previously expected. We identify the genetic syndromes associated with some cases of Chiari type I malformation, and we provide evidence in favor of a genetic hypothesis for at least a subset of the nonsyndromic cases.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The eighth cranial nerve Enterline, D S
Topics in magnetic resonance imaging,
06/1996, Volume:
8, Issue:
3
Journal Article
Peer reviewed
This review discusses the eighth cranial nerve with emphasis on magnetic resonance imaging (MRI). Normal anatomy of the component nerves as well as pathology that affects it are examined. MRI ...techniques used to evaluate this area are also presented.
Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of ...evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND Vitamin A (retinol), in the form of retinoic acid (RA), is essential for normal development of the human embryo. Studies in the mouse and zebrafish have shown that retinol is metabolized ...in the developing spinal cord and must be maintained in a precise balance along the anteroposterior axis. Both excess and deficiency of RA can affect morphogenesis, including failures of neural tube closure. METHODS We chose to investigate 5 genes involved in the metabolism or synthesis of RA, ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2, for their role in the development of human neural tube defects, such as spina bifida. RESULTS An association analysis using both allelic and genotypic single-locus tests revealed a significant association between the risk for spina bifida and 3 polymorphisms in the gene ALDH1A2; however, we found no evidence of a significant multilocus association. CONCLUSIONS These results may suggest that polymorphisms in ALDH1A2 may influence the risk for lumbosacral myelomeningocele in humans. Birth Defects Research (Part A), 2005.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neural tube defects are a common, complex disorder with genetic and environmental components to risk. We investigated the previously reported interaction between homozygosity for the thermolabile ...variant at the methylenetetrahydrofolate reductase and heterozygosity for the 844ins68 allele at the cystathionine β‐synthase loci in cases with lumbosacral myelomeningocele and their parents. Using control allele frequencies from our sample pooled with those published in the literature, we confirm a marginally significant interaction at these two loci. This finding suggests that additional, larger studies are warranted to investigate this possible interaction in more detail.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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