Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Strong protective effect of the p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Nephrotic Syndrome Gene Is Required for Endosomal Maturation and Nephrin Endocytosis in .

Background: Variants in cause nephrotic syndrome. TBC1D8B is a GTPase-activating protein for Rab11 (RAB11-GAP) that interacts with nephrin, but how it controls nephrin trafficking or other podocyte functions remains unclear.

Methods: We generated a stable deletion in and used microhomology-mediated end-joining for genome editing.

Autosomal Dominant Tubulointerstitial Kidney Disease-Uromodulin Misclassified as Focal Segmental Glomerulosclerosis or Hereditary Glomerular Disease.

Introduction: Focal segmental glomerulosclerosis (FSGS) is a histopathologically defined kidney lesion. FSGS can be observed with various underlying causes, including highly penetrant monogenic renal disease. We recently identified pathogenic variants of , a gene encoding the tubular protein uromodulin, in 8 families with suspected glomerular disease.

Contributions of Rare Gene Variants to Familial and Sporadic FSGS.

Background: Over the past two decades, the importance of genetic factors in the development of FSGS has become increasingly clear. However, despite many known monogenic causes of FSGS, single gene defects explain only 30% of cases.

Methods: To investigate mutations underlying FSGS, we sequenced 662 whole exomes from individuals with sporadic or familial FSGS.

Principles of genetic testing and genetic counseling for renal clinicians.

The advancement of genetic information and increased access to genetic testing options requires renal clinicians to expand their working knowledge of genetics and translate this information in a way that is meaningful to their patients. It is helpful to distinguish between the three types of genetic testing: clinical genetic testing, research genetic testing, and direct to consumer testing, and to communicate these differences to patients interested in these options. Although clinicians may not have the time to stage an entire genetic counseling session with each patient, the following scenarios offer tools and techniques from genetic counseling that can be used to facilitate the genetic testing process, foster client decision making, and to identify patients who may benefit from referral to a genetic counselor for additional support.

A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9.

Genetic variation at the MYH9 locus is linked to the high incidence of focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease among African Americans. To further define risk alleles with FSGS we performed a genome-wide association analysis using more than one million single-nucleotide polymorphisms in 56 African-American and 61 European-American patients with biopsy-confirmed FSGS. Results were compared to 1641 European Americans and 1800 African Americans as unselected controls.