New Report of a Different Clinical Presentation of &lt;b&gt;&lt;i&gt;CD151&lt;/i&gt;&lt;/b&gt; Splicing Mutation (c.351+2T&amp;#x3e;C): Could &lt;b&gt;&lt;i&gt;TSPAN11&lt;/i&gt;&lt;/b&gt; be Considered as a Potential Modifier Gene for &lt;b&gt;&lt;i&gt;CD151&lt;/i&gt;&lt;/b&gt;?

Rahmani, Nasim; Talebi, Saeed; Hoseini, Rozita; Kollahi, Neda Asghari; Shojaei, Azadeh

doi:10.1159/000519633

Cited by 2 publications

(1 citation statement)

References 26 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another example is family F7829 where one affected fetus was found to have bilateral renal agenesis and a homozygous LOF variant in CD151 (Fig. 2d ), which is typically linked to nephropathy rather than renal agenesis (one report of CD151 -related renal agenesis appeared after the initial submission 9 ). Dual molecular diagnosis was specifically investigated and excluded in families under this category.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families

AlAbdi,

Maddirevula,

Shamseldin

et al. 2023

Nat Commun

View full text Add to dashboard Cite

Despite large sequencing and data sharing efforts, previously characterized pathogenic variants only account for a fraction of Mendelian disease patients, which highlights the need for accurate identification and interpretation of novel variants. In a large Mendelian cohort of 4577 molecularly characterized families, numerous scenarios in which variant identification and interpretation can be challenging are encountered. We describe categories of challenges that cover the phenotype (e.g. novel allelic disorders), pedigree structure (e.g. imprinting disorders masquerading as autosomal recessive phenotypes), positional mapping (e.g. double recombination events abrogating candidate autozygous intervals), gene (e.g. novel gene-disease assertion) and variant (e.g. complex compound inheritance). Overall, we estimate a probability of 34.3% for encountering at least one of these challenges. Importantly, our data show that by only addressing non-sequencing-based challenges, around 71% increase in the diagnostic yield can be expected. Indeed, by applying these lessons to a cohort of 314 cases with negative clinical exome or genome reports, we could identify the likely causal variant in 54.5%. Our work highlights the need to have a thorough approach to undiagnosed diseases by considering a wide range of challenges rather than a narrow focus on sequencing technologies. It is hoped that by sharing this experience, the yield of undiagnosed disease programs globally can be improved.

show abstract

Section: Resultsmentioning

confidence: 99%

Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families

AlAbdi,

Maddirevula,

Shamseldin

et al. 2023

Nat Commun

View full text Add to dashboard Cite

show abstract

Identification of natriuretic peptide receptor A-related gene expression signatures in podocytes in vivo reveals baseline control of protective pathways

Jensen,

Heinl,

Federlein

et al. 2024

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Natriuretic peptide receptor-A (NPR-A) is the principal receptor for the natriuretic peptides ANP and BNP. Targeted deletion of NPR-A in mouse glomerular podocytes significantly enhances renal injury in vivo in the DOCA-salt experimental model. It was therefore hypothesized that natriuretic peptides exert a direct protective effect on glomerular barrier integrity through activation of NPR-A and modulation of gene expression patterns in podocytes. Green fluorescence-positive podocytes from mice with a conditional deletion of Npr1 encoding NPR-A were isolated by fluorescence-activated cell sorting. Differentially expressed genes (DEGs) in podocytes were identified by RNA sequencing of podocytes from wild-type and NPR-A deleted mice. Enrichment analysis was performed on the DEGs using Gene Ontology (GO) terms. Identified transcripts were validated by real-time PCR and ELISA of cultured isolated human and mouse glomeruli. In addition, the effect of natriuretic peptides on podocyte migration was investigated by measuring the outgrowth of podocytes from cultured glomeruli. A total of 158 DEGs were identified with 81 downregulated and 77 upregulated DEGs in Npr1 deficient podocytes. Among the downregulated genes were protein S and semaphorin 3G, which are known to have a protective effect in podocytes. Protein S was also expressed in and secreted from isolated human glomeruli. GO enrichment analysis revealed that the upregulated DEGs in NPR-A deficient podocytes were associated with cell migration and motility. In line, BNP significantly decreased podocyte outgrowth from cultured glomeruli. Endogenous levels of natriuretic peptides in mice support baseline protective pathways at glomerular podocytes such as protein S and suppress podocyte migration.

show abstract

New Report of a Different Clinical Presentation of <b><i>CD151</i></b> Splicing Mutation (c.351+2T>C): Could <b><i>TSPAN11</i></b> be Considered as a Potential Modifier Gene for <b><i>CD151</i></b>?

Cited by 2 publications

References 26 publications

Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families

Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families

Identification of natriuretic peptide receptor A-related gene expression signatures in podocytes in vivo reveals baseline control of protective pathways

Contact Info

Product

Resources

About