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Central nervous system: Paediatric and neurodevelopmental disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Hydrocephalus frequently accompanies spina bifida, and a careful check should be made before assuming that hydrocephalus is an isolated and primary phenomenon. The great majority of families do not follow a Mendelian pattern; an X-linked type with aqueduct stenosis exists but is extremely rare, and counselling as for an X-linked trait should only be given if the pedigree pattern is clearly X-linked or if the other characteristic features of this type are present. Mutations have been shown in this form in the L1CAM gene, involving a neural cell adhesion protein. The general recurrence risk for sibs of an isolated case of hydrocephalus is 1%–2%, 4%–5% for male sibs of an isolated male case, and around 8% where two sibs are affected. Where an isolated male case is due to aqueduct stenosis, the risk to male sibs has been shown to be somewhat higher, possibly 5%–10%, although this figure may be an overestimate.
The Cerebellar Ataxias and Hereditary Spastic Paraplegias
Published in John W. Scadding, Nicholas A. Losseff, Clinical Neurology, 2011
MASA syndrome leads to mental retardation, aphasia, shuffling gait and adducted thumbs. A spastic paraplegia develops later. A distinct form of X-linked complex HSP also maps to this locus as do X-linked hydrocephalus and X-linked corpus callosum agenesis. All are caused by mutations of the L1 gene, which encodes the L1 neural cell adhesion molecule (L1CAM). This gene is also referred to as SPG1.
Bodily-tactile early intervention for a mother and her child with visual impairment and additional disabilities: a case study
Published in Disability and Rehabilitation, 2023
Sini Peltokorpi, Saara Salo, Anne Nafstad, Paul Hart, Elsa Tuomikoski, Minna Laakso
Information related to Robin’s development and functioning of the senses was gathered from medical records and a parental interview. Robin was one year and five months old at the outset of the study. He had an L1CAM gene mutation causing L1 syndrome, with agenesis of the corpus callosum, obstructive hydrocephalus (with a shunt), adducted thumbs, epilepsy, and a mixed specific developmental disorder. Aside from L1 syndrome, Robin had a congenital VI that caused a 50% degree of visual disability. Moreover, he had strabismus and nystagmus. Robin was able to detect a toy when it was brought near him, but he could not see far or pictures in books. Robin used eyeglasses for half of the day. His hearing was normal. Robin was hypotonic and could not sit without support. During the time of the study, Robin’s family had five counselling sessions with a speech pathologist because of Robin’s eating difficulties. At the outset of the study, Robin had not had any support for communication. Robin’s 26-year-old mother is a healthcare professional.
Human endogenous retrovirus K (HERV-K) env in neuronal extracellular vesicles: a new biomarker of motor neuron disease
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022
Yuan Li, Yong Chen, Nan Zhang, Dongsheng Fan
Previous studies have used autopsy brain tissue, which is difficult to obtain, or detected HERV mRNA or antibodies in the blood, the origination of which cannot be confirmed. This study examined the level of HERV-K env in neuronal extracellular vesicles, suggesting that neuronal extracellular vesicles in blood can be used for noninvasive detection of HERV-K env expression in the central nervous system. Many previous studies have confirmed L1CAM is selective for extracellular vesicles derived from neurons. Fiandaca et al. (25) have verified the mouse anti-human L1CAM biotinylated antibody does not bind to NK and NKT cells of the immune system and is differently distributed in the nervous system. Winston et al. (26) used mouse anti-human L1CAM biotinylated antibody to extract neuron-derived exosomes in serum of AD patients. Jiang et al. (30) also chose anti-L1CAM antibodies to get extracellular vesicles with characteristics of exosomes and used mass spectrometry analysis and immunoblotting confirmed the presence of neural cell adhesion molecule and L1CAM. However, it cannot be ignored that L1CAM is reported in multiple studies to also be expressed in other tissues than neurons. We look forward to a more specific and precise method to extract EVS derived from neurons in the future.
Inhibiting L1CAM Reverses Cisplatin Resistance of Triple Negative Breast Cancer Cells by Blocking AKT Signaling Pathway
Published in Cancer Investigation, 2022
Lu-Yao Zhang, Zhi-Xin Shen, Lu Guo
In recent years, L1CAM has been considered as a biomarker of tumor progression and prognosis and also a potential target of tumor treatment, since it was expressed in various tumor cells and plays a vital role in tumor invasion and metastasis (16). Besides, clonal mutations densely distributed in urothelial carcinoma treated with chemotherapy were also found associated with the L1CAM signaling pathway (20). After treatment with carboplatin, vincristine, and etoposide, L1CAM deficiency significantly reduced the activity of retinoblastoma cells, while L1CAM over-expression increased the cell resistance to these drugs (16). Sebens Muerkoster et al. reported chemotherapy-sensitive pancreatic ductal adenocarcinoma cell lines (PDAC, PT45-P1) only expressed few L1CAM, while long-term drug therapy can increase the expression of L1CAM in drug-resistant pt45-p1res cells (21). Consistent with the above studies, the up-regulated L1CAM expression was also observed in drug-resistant TNBC cells (MDA-MB-231/DDP) when compared with their parental cells, suggesting that L1CAM over-expression may affect the DDP resistance of TNBC cells. More importantly, down-regulation of L1CAM can sensitize cells to DDP in ovarian cancer (22,23), intrahepatic cholangiocarcinoma (14), and melanoma (24). In the current study, MDA-MB-231/DDP cells underwent modification with the transfection of two L1CAM siRNAs, with the aim to prevent possible off-target effects. As demonstrated by the results, both L1CAM siRNA#1 and L1CAM siRNA#2 could significantly reduce IC50 of MDA-MB-231/DDP cells to DDP, which supported the hypothesis that silencing L1CAM can reverse the DDP resistance of TNBC.