Imaging in spine and spinal cord malformations

Rossi, Andrea; Biancheri, Roberta; Cama, Armando; Piatelli, Gianluca; Ravegnani, Marcello; Tortori-Donati, Paolo

doi:10.1016/j.ejrad.2003.10.015

Cited by 126 publications

(140 citation statements)

References 44 publications

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“…This leads to a p.Val1386Leu substitution that is conservative as both residues have very similar structures. The variant c.4622G.T was detected in an 11-year-old female affected with a severe form of closed NTDs called caudal agenesis that represents a heterogeneous constellation of anomalies comprising total or partial agenesis of the spinal column, anal imperforation, genital anomalies, bilateral renal dysplasia or aplasia, pulmonary hypoplasia and lower limb abnormalities (12). This variant changes a highly conserved tyrosine at position 1541 in the cytoplasmic domain of LRP6 between the second and third PPPSP phosphorylation motifs and leads to a non-conservative p.Tyr1541Cys substitution.…”

Section: Lpmentioning

confidence: 99%

“…The most common forms of NTDs are referred to as open NTDs and include anencephaly and myelomeningocele (spina bifida), which result from the failure of fusion in the cranial and spinal region of the neural tube, respectively (9). A number of skin-covered (closed) NTDs are categorized clinically depending on the presence (including lipomyeloschisis, lipomyelomeningocele and meningocele) or absence of a subcutaneous mass (including dermal sinus and caudal agenesis) (12). Population and family studies indicate a complex etiology to NTDs involving environmental and genetic factors.…”

Section: Introductionmentioning

confidence: 99%

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Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway

Allache

Lachance

Guyot

et al. 2013

Human Molecular Genetics

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Wnt signaling has been classified as canonical Wnt/b-catenin-dependent or non-canonical planar cell polarity (PCP) pathway. Misregulation of either pathway is linked mainly to cancer or neural tube defects (NTDs), respectively. Both pathways seem to antagonize each other, and recent studies have implicated a number of molecular switches that activate one pathway while simultaneously inhibiting the other thereby partially mediating this antagonism. The lipoprotein receptor -related protein Lrp6 is crucial for the activation of the Wnt/b-catenin pathway, but its function in Wnt/PCP signaling remains largely unknown. In this study, we investigate the role of Lrp6 as a molecular switch between both Wnt pathways in a novel ENU mouse mutant of Lrp6 (Skax26 m1Jus ) and in human NTDs. We demonstrate that Skax26 m1Jus represents a hypermorphic allele of Lrp6 with increased Wnt canonical and abolished PCP-induced JNK activities. We also show that Lrp6Skax26-Jus genetically interacts with a PCP mutant (Vangl2 Lp ) where double heterozygotes showed an increased frequency of NTDs and defects in cochlear hair cells' polarity. Importantly, our study also demonstrates the association of rare and novel missense mutations in LRP6 that is an inhibitor rather than an activator of the PCP pathway with human NTDs. We show that three LRP6 mutations in NTDs led to a reduced Wnt canonical activity and enhanced PCP signaling. Our data confirm an inhibitory role of Lrp6 in PCP signaling in neurulation and indicate the importance of a tightly regulated and highly dosage-sensitive antagonism between both Wnt pathways in this process.

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Section: Lpmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway

Allache

Lachance

Guyot

et al. 2013

Human Molecular Genetics

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“…La segunda neurulación da origen al cono medular, al filum terminale y a los precursores del sacro-coxis. Finalmente, en la tercera etapa o de regresión, se produce el ascenso de la médula espinal a la posición normal del adulto entre L1-L2 (1,(3)(4)(5). Las alteraciones en la inducción dorsal son consecuencia del cierre incompleto del tubo neural, situación que origina la persistencia de comunicación entre el ectodermo posterior y el ectodermo cutáneo, lo que se conoce como "Disrafismo espinal" (2,3,5).…”

Section: Discussionunclassified

“…Cuando la malformación afecta solamente a las vértebras (falta de fusión de los arcos posteriores vertebrales), se denomina espina bífida oculta, pero cuando el defecto involucra a las estructuras óseas junto con meninges y/o médula espinal, sin afectación de la piel, se denomina disrafismo espinal oculto, pudiendo incluirse bajo esta denominación patologías variadas como: Médula anclada (la más frecuente), quistes epidermoides, dermoides, lipoma lumbosacro, quiste entérico intraespinal, diastematomielia y mielocistocele terminal (1,(3)(4)(5)(6). En la espina bífida quística o abierta, la ausencia de fusión de partes óseas y blandas permite que las meninges, médula espinal y raíces nerviosas estén abiertas en contacto con el exterior.…”

Section: Discussionunclassified

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Meningocele Anterior Sacro: A Propósito de un Caso

Sartori

Díaz

Caraballo

2013

Ciencia e Innovación en Salud

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RESUMENEl meningocele anterior sacro oculto es un disrafismo espinal de presentación infrecuente. Se origina por la protrusión de un saco dural, a través de un defecto óseo en la pared sacra anterior, que se localiza en el espacio extraperitoneal presacro. Su etiología es multifactorial y generalmente asintomática, pudiendo asociarse a otras patologías urogenitales, digestivas y ortopédicas. Se diagnostica en forma incidental como una masa homogénea pelviana que contiene duramadre y, ocasionalmente, estructuras nerviosas. En este trabajo, presentamos un caso de meningocele anterior sacro oculto asintomático. Palabras Clave: Meningocele, disrafismo espinal. (Fuente: DeCS). ABSTRACTOccult anterior sacral meningocele is considered as a rare spinal dysraphism. It is caused by the protrusion of a dural sac, through a bone defect in the anterior sacral wall, which is located in the peritoneal space or presacral space. Its ethiology is multifactorial and asymptomatic generally, and it may be associated with other urogenital, digestive and orthopaedic pathologies. It is diagnosed as a homogenous pelvic mass incidentally that contains dura mater and, neural structures occasionally. In this paper, we show a case of asymptomatic occult anterior sacral meningocele.

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Planar cell polarity gene mutations contribute to the etiology of human neural tube defects in our population

Marco

Merello

Piatelli

et al. 2014

Birth Defects Research

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Neural Tube Defects (NTDs) are congenital malformations that involve failure of the neural tube closure during the early phases of development at any level of the rostro-caudal axis. The planar cell polarity (PCP) pathway is a highly conserved, noncanonical Wnt-Frizzled-Dishevelled signaling cascade, that was first identified in the fruit fly Drosophila. We are here reviewing the role of the PCP pathway genes in the etiology of human NTDs, updating the list of the rare and deleterious mutations identified so far. We report 50 rare nonsynonymous mutations of PCP genes in 54 patients having a pathogenic effect on the protein function. Thirteen mutations that have previously been reported as novel are now reported in public databases, although at very low frequencies. The mutations were private, mostly missense, and transmitted by a healthy parent. To date, no clear genotype-phenotype correlation has been possible to create. Even if PCP pathway genes are involved in the pathogenesis of neural tube defects, future studies will be necessary to better dissect the genetic causes underlying these complex malformations.

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Imaging in spine and spinal cord malformations

Cited by 126 publications

References 44 publications

Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway

Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway

Meningocele Anterior Sacro: A Propósito de un Caso

Planar cell polarity gene mutations contribute to the etiology of human neural tube defects in our population

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