Investigating Skeletal Anomalies (<i>LIFR</i> Gene Mutations) in Three Khuzestan Families with Whole-Exome Sequencing

Abstract

Background: Stuve-Wiedemann syndrome (SWS; OMIM #601559) is a rare skeletal disorder characterized by abnormal bone curvature, respiratory problems, feeding difficulties, and episodes of high body temperature. While SWS typically leads to infant mortality, some individuals may survive into adolescence and occasionally beyond. This condition results from mutations in the leukemia inhibitory factor receptor (LIFR) gene, which follows an autosomal recessive inheritance pattern. The majority of LIFR mutations associated with SWS are nonsense mutations that lead to mRNA instability, hinder LIFR production, and disrupt the crucial JAK/STAT3 signaling pathway. Objectives: The objective of this investigation is to gain a deeper understanding of the genetic aspects of this uncommon disorder. Methods: In this study, initially, 5 cc of peripheral blood was collected from the patients. Then, using the salting out method, the genetic material of the patients was extracted and sent for whole-exome sequencing (WES) testing. This study was registered with the code of ethics IR.IAU.D.REC.1403.016 at Islamic Azad University, Dezful Branch. Results: Three families from Khuzestan province were screened for the presence of this rare disease. Screening revealed the presence of a new variant for the LIFR gene (NM_001127671: exon9: c. A1267G: p.I423V) in one of the patients. This variant was not found in the other two families. The obtained variant was also confirmed in the patient's parents using the Sanger technique. Conclusions: This study shows the importance of using the new NGS technique in finding potential pathogenic variants in rare diseases and diagnosing the genetic origin of bone abnormalities.