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Identification and in silico structural analysis for the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: case report and developmental insight using microsatellite markers.

Authors :
Hosseini Nami A
Kabiri M
Zafarghandi Motlagh F
Shirzadeh T
Bagherian H
Zeinali R
Karimi A
Zeinali S
Source :
Therapeutic advances in respiratory disease [Ther Adv Respir Dis] 2024 Jan-Dec; Vol. 18, pp. 17534666241253990.
Publication Year :
2024

Abstract

Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and in silico studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the de novo nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The de novo mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to in silico structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of de novo mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population.

Details

Language :
English
ISSN :
1753-4666
Volume :
18
Database :
MEDLINE
Journal :
Therapeutic advances in respiratory disease
Publication Type :
Academic Journal
Accession number :
38904297
Full Text :
https://doi.org/10.1177/17534666241253990