The mutation-dependent pathogenicity of NPHS2 p.R229Q: A guide for clinical assessment
| Autor: | Dóra K. Menyhárd, Kálmán Tory, Ágnes Mikó, Ambrus Kaposi, Corinne Antignac |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Nephrotic Syndrome Protein Conformation Population Amino Acid Motifs 030232 urology & nephrology Biology medicine.disease_cause Polymorphism Single Nucleotide Risk Assessment 03 medical and health sciences 0302 clinical medicine Focal segmental glomerulosclerosis Gene Frequency Genetics medicine Humans Genetic Predisposition to Disease education Allele frequency Genetics (clinical) Mutation education.field_of_study Glomerulosclerosis Focal Segmental Intracellular Signaling Peptides and Proteins Membrane Proteins medicine.disease Major gene 030104 developmental biology Podocin biology.protein Trans-acting Protein Multimerization Nephrotic syndrome |
| Zdroj: | Human mutation. 39(12) |
| ISSN: | 1098-1004 |
| Popis: | NPHS2, encoding podocin, is the major gene implicated in steroid-resistant nephrotic syndrome. Its c.686G>A, p.R229Q variant is the first human variant with a mutation-dependent pathogenicity; it is only pathogenic when trans-associated to specific mutations. Secondary to its high allele frequency in the European, South Asian, African, and Latino populations, its benign trans-associations can be accidentally identified in affected patients. Distinguishing pathogenic and benign p.R229Q associations can be challenging. In this paper, we present the currently known pathogenic and benign associations, and show that a rare p.R229Q association can be considered pathogenic if the variant in trans meets the following criteria; it affects the 270-351 residues and alters but does not disrupt the oligomerization, its p.R229Q association is found in a family with slowly progressing focal segmental glomerulosclerosis, but is expected to be rare in the general population ( 15% of the p.R229Q associations identified so far in patients are benign. |
| Databáze: | OpenAIRE |
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