Nearly all children with PSC have rare, deleterious genetic variants

SAN FRANCISCO — Researchers found deleterious variants in nearly all children presenting with primary sclerosing cholangitis, according to a poster presentation at The Liver Meeting 2015.

“Patients with childhood-onset [primary sclerosing cholangitis] harbor rare, deleterious variants in genes involved with cholestasis and risk of [primary sclerosing cholangitis], suggesting that disease in these patients may lie along a spectrum between syndromic forms of cholestatic disease and classical [primary sclerosing cholangitis],” Brian D. Juran, and colleagues from the Mayo Clinic, Rochester, Minnesota, wrote in their abstract.

Juran and colleagues looked at 10 patients with childhood-onset primary sclerosing cholangitis (PSC) and analyzed their genome for single nucleotide variants (SNVs) among 28 known cholestasis genes or the 15 PSC genome-wide association study (GWAS)-implicated genes. Lastly, the researchers looked specifically at those SNVs considered rare, defined as population minor allele frequency less than 1.5%, and those expected to have functional impact, as defined by at least one of three predictive tools.

After filtering, the researchers found 14 specific SNVs, nine of which were from known cholestasis genes ABCB4, ABCC2, HSD3B7, NOTCH2, SERPINA1 and TJP2, and five of which were from the GWAS list: CD226, GPR35, MST1 and SH2B3.

Of the 10 patients studied, nine had at least one SNV, with four having one SNV, four having two SNVs and one having three SNVs.

“Additional studies, including patients with more-typical disease onset, will help to confirm this finding and may establish a role for these genes in adult disease,” the researchers wrote. – by Katrina Altersitz

Reference:

Juran BD, et al. Abstract 600. Presented at: The Liver Meeting; Nov. 13-17, 2015; San Francisco.

Disclosures: The researchers report no relevant financial disclosures.