"LINGO1"

Biallelic variants in LINGO1 are associated with autosomal recessive intellectual disability, microcephaly, speech and motor delay. To elucidate the novel molecular cause in two unrelated consanguineous families with autosomal recessive intellectual disability. A combination of homozygosity mapping and exome sequencing was used to locate the plausible genetic defect in family F162, while only exome sequencing was followed in the family PKMR65. The protein 3D structure was visualized with the University of California-San Francisco Chimera software. All five patients from both families presented with severe intellectual disability, aggressive behavior, and speech and motor delay. Four of the five patients had microcephaly. We identified homozygous missense variants in LINGO1, p.(Arg290His

Increased LINGO1 in the cerebellum of essential tremor patients. Essential tremor (ET) is the most prevalent adult-onset movement disorder. Despite its health burden, no clear pathognomonic sign has been identified to date because of the rarity of clinicopathological studies. Moreover, treatment options are still scarce and have not significantly changed in the last 30 years, underscoring the urgent need to develop new treatment avenues. In the recent years, leucine-rich repeat (LRR) and immunoglobulin (Ig) domain-containing Nogo receptor-interacting proteins 1 and 2 (LINGO1 and LINGO2, respectively) have been increasingly regarded as possible ET modulators due to emerging genetic association studies linking LINGO with ET. We have investigated LINGO protein and messenger RNA (mRNA

LINGO1 rs9652490 and rs11856808 polymorphisms are not associated with risk for multiple sclerosis. Some recent experimental data suggest a possible role of LINGO-1 in the pathogenesis of multiple sclerosis (MS). In an attempt to identify genetic biomarkers related to MS susceptibility, we genotyped two common SNPs in the LINGO1 gene which have been associated to other neurological conditions , in patients with MS and in healthy subjects. These SNPs are linked to several SNPs within the LINGO1 gene, especially in individuals of Oriental or Caucasian descent. We analyzed the allelic and genotype frequency of two LINGO1 variants (rs9652490 and rs11856808) in 293 patients with MS and 318 healthy controls, using KASPar assays. LINGO1 rs9652490 and rs11856808 allelic and genotype frequencies did

the expression of miR-219 or miR-338 in the serum exosomes of mice with EAE, thereby suppressing the expression of Sox6, Lingo1, and Hes5, which negatively regulate OPCs differentiation. Therefore, serum exosomes of BSYSC-treated mice (exos-BSYSC) were extracted and administered to OPCs in which miR-219 or miR-338 expression was knocked down by adenovirus, and the results showed that Sox6, Lingo1, and Hes5

 = 4.96*10 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric

targets in oligodendrocytes and further uncover a novel network for miR-219 targeting of differentiation inhibitors including Lingo1 and Etv5. Inhibition of Lingo1 and Etv5 partially rescues differentiation defects of miR-219-deficient oligodendrocyte precursors. Furthermore, miR-219 mimics enhance myelin restoration following lysolecithin-induced demyelination as well as experimental autoimmune

, 2016), in order to prevent neurological disability in MS (Irvine and Blakemore, 2008; Patrikios, 2006; Duncan I, 2017, Bodini, 2016).Among the first candidate compounds developed to promote remyelination was the anti Lingo1 antibody, which enhance remyelination (Mi, 2009). Medium and large throughput screening of drug libraries subsequently identified several chemical classes of compounds with strong

in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.

revealed a specific surfaceome of Ewing and showed unexpectedly that the leucine-rich repeat and Ig domain protein 1 (LINGO1) is expressed in over 90% of Ewing sarcoma tumors, but not expressed in any other somatic tissue apart from the brain. We found that the LINGO1 protein acts as a gateway protein internalizing into the tumor cells when engaged by antibody and can carry antibody conjugated with drugs to kill Ewing sarcoma cells. Therefore, LINGO1 is a new, unique, and specific biomarker and drug target for the treatment of Ewing sarcoma.

. 129:2318-31. [QxMD MEDLINE Link]. 24. Higgins JJ, Lombardi RQ, Pucilowska J, Jankovic J, Tan EK, Rooney JP. A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology. 2005 Feb 8. 64(3):417-21. [QxMD MEDLINE Link]. 25. Thier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor in Europeans. Mov Disord. 2010 Apr 30 . 25(6):717-23. [QxMD MEDLINE Link]. 26. Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet. 2010 Jul. 18(7):838-43. [QxMD MEDLINE Link]. [Full Text]. 27. Tan EK, Teo YY, Prakash KM, et al. LINGO1 variant increases risk of familial essential tremor. Neurology

to a region on chromosome 6p23. Brain. 2006 Sep. 129:2318-31. [QxMD MEDLINE Link]. 24. Higgins JJ, Lombardi RQ, Pucilowska J, Jankovic J, Tan EK, Rooney JP. A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology. 2005 Feb 8. 64(3):417-21. [QxMD MEDLINE Link]. 25. Thier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor in Europeans. Mov Disord. 2010 Apr 30. 25(6):717-23. [QxMD MEDLINE Link]. 26. Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet. 2010 Jul. 18(7):838-43. [QxMD MEDLINE Link]. [Full Text]. 27. Tan EK, Teo YY, Prakash KM, et al. LINGO1 variant increases risk

. 129:2318-31. [QxMD MEDLINE Link]. 24. Higgins JJ, Lombardi RQ, Pucilowska J, Jankovic J, Tan EK, Rooney JP. A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology. 2005 Feb 8. 64(3):417-21. [QxMD MEDLINE Link]. 25. Thier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor in Europeans. Mov Disord. 2010 Apr 30 . 25(6):717-23. [QxMD MEDLINE Link]. 26. Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet. 2010 Jul. 18(7):838-43. [QxMD MEDLINE Link]. [Full Text]. 27. Tan EK, Teo YY, Prakash KM, et al. LINGO1 variant increases risk of familial essential tremor. Neurology

, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor in Europeans. Mov Disord. 2010 Apr 30. 25(6):717-23. [QxMD MEDLINE Link]. 26. Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet. 2010 Jul. 18(7):838-43. [QxMD MEDLINE Link]. [Full Text]. 27 . Tan EK, Teo YY, Prakash KM, et al. LINGO1 variant increases risk of familial essential tremor. Neurology. 2009 Oct 6. 73(14):1161-2. [QxMD MEDLINE Link]. [Full Text]. 28. Dogu O, Sevim S, Camdeviren H, et al. Prevalence of essential tremor: door-to-door neurologic exams in Mersin Province, Turkey. Neurology. 2003 Dec 23. 61(12):1804-6. [QxMD MEDLINE Link]. 29. Louis ED, Barnes

SLC1A2 variant associated with essential tremor but not Parkinson disease in Chinese subjects. Essential tremor (ET) is characterized by postural and action tremor.(1-3) A genome-wide association study (GWAS) identified a LINGO1 gene variant to be associated with ET.(4) Subsequent GWAS further identified an intronic variant (rs3794087) of the main glial glutamate transporter (SLC1A2) gene to be associated with ET with an odds ratio (OR) of approximately 1.4.(5) We conducted a case-control study to examine the SLC1A2 gene variant in an Asian cohort of ET. In addition, we also investigated the variant in patients with Parkinson disease (PD) because the GWAS LINGO1 variant has been implicated in both ET and PD and etiologic links between the conditions have been suggested.(6.)

regarding several genes (NAV2, EFCAB11/TDP1, AGBL1, PTPN9, LINGO1 and LOC730118), with the strongest association at rs4143999 near EFCAB11/TDP1 (p=0.00001 for carotid presence and 0.00003 for plaque area, multiple testing corrected p≤0.02). The association in AGBL1 and PTPN9 was mainly driven by the families with linkage evidence (p=0.00008-0.00001 and 0.76-0.32, respectively, in the families

Replication of the LINGO1 gene association with essential tremor in a North American population. A marker in the LINGO1 gene, rs9652490, showing significant genome-wide association with essential tremor (ET), was recently reported in an Icelandic population. To replicate this association in an independent population from North America, we genotyped 15 SNPs in the LINGO1 gene in 257 Caucasian ET that the LINGO1 gene is a risk factor for ET in a Caucasian population in North America, and further shows that those with early-onset ET are likely to be at high risk.

Variant in the sequence of the LINGO1 gene confers risk of essential tremor. We identified a marker in LINGO1 showing genome-wide significant association (P = 1.2 x 10(-9), odds ratio = 1.55) with essential tremor. LINGO1 has potent, negative regulatory influences on neuronal survival and is also important in regulating both central-nervous-system axon regeneration and oligodendrocyte maturation . Increased axon integrity observed in Lingo1 mouse [corrected] knockout models highlights the potential role of LINGO1 in the pathophysiology of ET [corrected]

LINGO1 polymorphisms are associated with essential tremor in Europeans. Essential tremor (ET) is one of the most common movement disorders. Former association studies focussing on candidate genes in ET found a number of risk variants but most of them were not replicated. Recently, a genome-wide association study revealed two intronic sequence variants in the LINGO1 gene associated with ET. Here , we have confirmed association between sequence variants in the LINGO1 gene and the ET phenotype in independent German and French ET samples. The odds ratios for the identified intronic markers rs8030859 (P = 1.0x10(-4)), rs9652490 (P = 9.1x10(-4)), and rs11856808 (P = 3.6x10(-2)) were 1.72 (CI 1.31-2.26), 1.61 (CI 1.21-2.14), and 1.30 (CI 1.02-1.66), respectively, in our German sample. LINGO1

Role of LINGO1 polymorphisms in Parkinson's disease. A clinical overlap between Parkinson's disease (PD) and essential tremor (ET) has prompted a discussion whether these conditions share common genetic susceptibility factors. Recently, the first genome-wide association study in ET revealed a significant association with a variant in the LINGO1 gene. LINGO1 has also been demonstrated to play a role in the survival of dopaminergic neurons in an animal model of PD, and therefore constitutes a potential candidate gene for PD. In this study, SNPs rs9652490, rs11856808, and rs7177008 of LINGO1 were genotyped in a total of 694 Austrian subjects (349 PD, 345 controls). No association could be found between genotype or allele counts and PD. Neither did a subgroup analysis in tremor-dominant

LINGO1 gene analysis in Parkinson's disease phenotypes. Parkinson's disease (PD) and essential tremor (ET) may share some etiopathogenic factors. A genome-wide association study has shown that LINGO1 gene variants are associated with increased risk of ET. We hypothesized that LINGO1 variants could increase susceptibility to PD. A large series of PD subjects and healthy controls were genotyped for rs9652490 and rs11856808 LINGO1 single nucleotide polymorphisms (SNPs). We found an increased frequency of the rs11856808(T/T) genotype in PD compared with controls (odds ratio = 1.46; corrected P value = 0.02). A recessive genetic model was the best fit for rs11856808 influence on PD (recessive gene action test: corrected P value = 0.01). Stratification analysis showed that rs11856808(T/T) genotype