A novel CFTR gene variant - p.Tyr517* associated with cystic fibrosis: a case report

Cystic fibrosis (CF) is a genetic disease usually diagnosed by clinical findings and abnormal sweat chloride testing.

We report a case of an 18-month-old Indian female with clinical findings suggestive of CF referred for genetic confirmation. The CFTR gene was sequenced for 23 mutations as per American College of Medical Genetics (ACMG) guidelines for CF and showed presence of a known common heterozygous delF508 (c.1521_1523delCTT, p.Phe508 del) variant. In addition to delF508 variant, exon 10 of CFTR gene also showed a novel variant c.1551C > G, p.Tyr517*, which was classified as "likely pathogenic" based on recent ACMG variant classification guidelines. The presence of compound heterozygous pathogenic variants along with classical clinical findings, confirmed the diagnosis of CF in this patient.

The novel pathogenic variants (missense/nonsense/deletion/duplication) in CFTR gene are often identified and are associated with CF, thus highlighting the need of comprehensive complete CFTR gene analysis.