Case report of compound CFTR variants in Korean siblings with cystic fibrosis: importance of differentiating cystic fibrosis from inflammatory bowel disease

Abstract

The prevalence of cystic fibrosis (CF) is considerably lower in Asian populations compared with that of Caucasians. Cases of CF are typically due to mutations in the CF transmembrane conductance regulator gene with autosomal recessive inheritance. Here, we report two cases of newly diagnosed CF in Korea-a 13-year-old boy and his 5-year-old brother. The older brother was admitted to our hospital for evaluation and treatment of recurrent abdominal pain, frequent diarrhea, and failure to thrive. Fecal calprotectin (FC) was elevated, and when combining this with his clinical presentation, inflammatory bowel disease (IBD) or eosinophilic gastroenteritis (EoGE) was the first impression of his disease. Several ulcerative lesions were observed on ileocolonoscopy. However, incidental findings of suspicious bronchiectatic lesions were observed on plain radiography, which were confirmed by chest computed tomography. Moreover, diffuse bowel wall thickening with pancreatic atrophy was also incidentally detected by computed tomography of the abdomen. Comprehensively, these findings were highly suggestive of CF. Therefore, diagnostic exome sequencing was conducted, which revealed compound heterozygous variants of c.263T>G (p.Leu88*) and c.2977G>T (p.Asp993Tyr) in the CF transmembrane conductance regulator gene. Although symptoms in the younger brother were not as prominent as the older brother, genetic test was also conducted, which revealed the same mutation. We report the identification of a novel variant, p.Asp993Tyr, in siblings with Korean heritage. Although CF is rare in Koreans, it should be included in the differential diagnosis of IBD.

Keywords: CF transmembrane conductance regulator gene (CFTR gene); Cystic fibrosis (CF); case report; diagnostic exome sequencing; inflammatory bowel disease (IBD).