Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases

Zm, Wang; Jq, Luo; Ly, Xu; Hh, Zhou; Zhang, W

doi:10.1038/tpj.2017.28

Cited by 26 publications

(13 citation statements)

References 81 publications

(92 reference statements)

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“…34 Lrp6 mimics WNT activity in enhancing neural crest formation,35 which gives rise to diverse cell lineages including cranioneural crest cells. LRP6 mutations are associated with congenital neural tube defects,36 37 and severe tooth agenesis,38 sometimes with CLP 39.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes

Basha¹,

Demeer²,

Revençu³

et al. 2018

J Med Genet

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These data demonstrate that patients with CL/P without cardinal signs of a syndrome may still carry a mutation in a gene linked to syCL/P. Rare coding and non-coding variants in syCL/P genes could in part explain the controversial question of 'missing heritability' for nsCL/P. Therefore, gene panels designed for diagnostic testing of syCL/P should be used for patients with nsCL/P, especially when there is at least third-degree family history. This would allow a more precise management, follow-up and genetic counselling. Moreover, stratified cohorts would allow hunting for genetic modifiers.

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Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes

Basha¹,

Demeer²,

Revençu³

et al. 2018

J Med Genet

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“…LRP6 may be involved in the onset of neurodegeneration through dysfunctions of long-term potentiation and immune activation. Abnormal LRP6 could also result in amyloid production and aggregation [134,135]. Espinosa et al (2018) also examined several additional genes among MCI patients and screened for their cognitive functions.…”

Section: Genetic Factors Which Could Increase the Risk For Mci-admentioning

confidence: 99%

Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

Giau

Bagyinszky

2019

IJMS

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Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person’s age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer’s disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of Aβ40, Aβ42, total tau and phosphorylated tau are useful for predicting the risk of progression from MCI to AD. This review highlights the advantages of the current blood-based biomarkers in MCI, and discusses some of these challenges, with an emphasis on recent studies to provide an overview of the current state of MCI.

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“…As the common GRHL3 variants identified as risk factors for NSCPO in European, Asian, and African populations ( Leslie et al, 2016 ; Mangold et al, 2016 ; Wang Y. et al, 2016 ) were not confirmed in our previous study, it is suggested that NSCPO risk associated with particular variants in GRHL3 may differ among ethnic groups and the variant identified in this study (rs34637004) may be the risk variant for the Brazilian population. LRP6 , which encodes a central co-receptor in the WNT/β-catenin signaling pathway, has pleiotropic roles in both normal development and complex diseases ( Wang et al, 2018 ). LRP6 controls the canonical WNT/β-catenin pathway promoting development of neural crests and participating in the craniofacial morphogenesis, including lip and palate formation ( Tamai et al, 2000 ; Song et al, 2009 ; Jin et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only

Machado

Martelli‐Júnior

Reis

et al. 2021

Front. Cell Dev. Biol.

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The identification of genetic risk factors for non-syndromic oral clefts is of great importance for better understanding the biological processes related to this heterogeneous and complex group of diseases. Herein we applied whole-exome sequencing to identify potential variants related to non-syndromic cleft palate only (NSCPO) in the multiethnic Brazilian population. Thirty NSCPO samples and 30 sex- and genetic ancestry-matched healthy controls were pooled (3 pools with 10 samples for each group) and subjected to whole-exome sequencing. After filtering, the functional affects, individually and through interactions, of the selected variants and genes were assessed by bioinformatic analyses. As a group, 399 variants in 216 genes related to palatogenesis/cleft palate, corresponding to 6.43%, were exclusively identified in the NSCPO pools. Among those genes are 99 associated with syndromes displaying cleft palate in their clinical spectrum and 92 previously related to cleft lip palate. The most significantly biological processes and pathways overrepresented in the NSCPO-identified genes were associated with the folic acid metabolism, highlighting the interaction between LDL receptor-related protein 6 (LRP6) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) that interconnect two large networks. This study yields novel data on characterization of specific variants and complex processes and pathways related to NSCPO, including many variants in genes of the folate/homocysteine pathway, and confirms that variants in genes related to syndromic cleft palate and cleft lip-palate may cause NSCPO.

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Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases

Cited by 26 publications

References 81 publications

Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes

Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes

Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only

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