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LIMS1 Genotyping Assay

Background:

Genetic mutation, including truncating or deletions, may lead to alterations in protein expression, conformation, or partial to complete absence of a protein.  As these genetic alterations have the potential to add or remove antigenic epitopes, they may be of consequence in transplant rejection. 

The LIMS1 protein (LIM zinc finger containing protein 1) is normally expressed in renal tissue.  Homozygous segmental deletion of an intergenic region downstream of the LIMS1 gene (CNVR915.1) in a renal transplant candidate has recently been found to be associated with an increased risk (~60%) of renal allograft rejection when the donor kidney has at least one non-deleted copy of the intergenic region (see reference below).  The precise mechanism of this effect is not currently known with certainty, but is felt to represent a minor histocompatibility antigen. This 1.5 kilobase (kb) deletion is in complete linkage disequilibrium (i.e. tightly linked) to the presence of a guanine (G) nucleotide at the upstream intronic locus chr2:108606280 (GRCh38.p12).  In contrast, the presence of an adenine (A) nucleotide at this locus is associated with absence of the downstream segmental deletion.  Detection of the nucleotide present at this SNP locus (rs893403) is therefore a marker for the presence (G) or absence (A) of the downstream segmental deletion of the LIMS1 gene, and provides a simple and reliable marker for genetic testing.  The average allele frequency for the G and A nucleotides at this locus is approximately 0.37 and 0.63 across East Asian, Latino, European, African, and Ashkenazi Jewish populations, and is rare in South Asians (gnomAD data base).

Reasons for Testing:

Detection of G (guanine) versus A (adenine) single nucleotide polymorphism (SNP; rs893403) upstream of the LIMS1 gene

If the anticipated allograft recipient is homozygous G/G at this locus, testing of a potential donor’s risk allele status determines if there is an increased risk of renal allograft rejection due “genomic collision” from this LIMS1 minor histocompatibility locus

Recipient G/G   Donor A/G or AA Increased risk of allograft rejection
Recipient G/A or AA  Donor G/G, A/G or AA No increased risk of allograft rejection
Recipient G/G   Donor G/G  No increased risk of allograft rejection

Test Details:

Method: real-time PCR (endpoint analysis)

Turnaround time: same-day

Acceptable specimens include:

Peripheral blood (preferred): At least 2 ml in Lavender top (EDTA) tube shipped overnight at room temperature

Previously extracted DNA (from CLIA certified lab): 10ul suspended in TE buffer at 10-100 ng/ul

Samples must have two patient identifiers, preferably the patient’s name and date of birth.

Each sample must be accompanied by a requisition form with the declaration signed by the ordering provider.

Shipping Instructions:

Please call Arkana Laboratories to request a kit

References:

Steers NJ, et al. Genomic Mismatch at LIMS1 Locus and Kidney Allograft Rejection. NEJM 2019;380:1918-1928

Contact Information:

Arkana Laboratories Molecular Division
10810 Executive Center Drive, Suite 100
Little Rock, AR 72211

Co-Director: Chris Larsen, MD
Co-Director: Jon D. Wilson, MD
Lab Manager: Marjorie Beggs, PhD