Genotype-phenotype correlations of cystic fibrosis in siblings compound heterozygotes for rare variant combinations: Review of literature and case report

Tinatin Tkemaladze; Eka Kvaratskhelia; Mariam Ghughunishvili; Michael J Lentze; Elene Abzianidze; Volha Skrahina; Arndt Rolfs

doi:10.1016/j.rmcr.2022.101750

Genotype-phenotype correlations of cystic fibrosis in siblings compound heterozygotes for rare variant combinations: Review of literature and case report

Respir Med Case Rep. 2022 Oct 5:40:101750. doi: 10.1016/j.rmcr.2022.101750. eCollection 2022.

Authors

Tinatin Tkemaladze^{1

2}, Eka Kvaratskhelia¹, Mariam Ghughunishvili^{1

2}, Michael J Lentze³, Elene Abzianidze¹, Volha Skrahina^{4

5}, Arndt Rolfs^{4

5

6}

Affiliations

¹ Department of Molecular and Medical Genetics, Tbilisi State Medical University, Georgia.
² Department of Pediatrics, Givi Zhvania Pediatric Academic Clinic, Tbilisi State Medical University, Georgia.
³ Department of Pediatrics, Children's Hospital Medical Center, University Hospitals Bonn, Germany.
⁴ Centogene GmbH, Rostock, Germany.
⁵ Arcensus, GmbH Rostock, Germany.
⁶ University of Rostock, Medical Faculty, Rostock, Germany.

Abstract

Here, we describe a cystic fibrosis (CF) family with affected siblings, two of whom have a combination of I1234V and 1677delTA variants with classic CF features, the third child with a combination of I1234V and L997F variants with atypical CF, and the apparently healthy mother with a combination of 1677delTA and L997F alleles. Interestingly, the sibling with I1234V and L997F variants had normal sweat test results and had a much milder phenotype than the other two siblings with I1234V and 1677delTA variants, suggesting that this combination is causative for atypical CF. The fact that their mother with the combination of 1677delTA and L997F appears to be healthy suggests that the L997F variant causes different phenotypes in different allele combinations. The current cases show that there is a genotype-phenotype correlation in this disease and underline the importance of genotyping individuals with suspected CF to allow prediction of disease severity and effective treatment.

Keywords: 1677delTA; CF; Cystic fibrosis (CF); Cystic fibrosis transmembrane conductance regulator (CFTR); I1234V; L997F; Sweat chloride.

Publication types

Case Reports