The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 12 - 2024 |
doi: 10.3389/fped.2024.1425030
Identification of a Novel FERMT1 Variant Causing Kindler Syndrome and a Review of the Clinical and Molecular Genetic Features in Chinese Patients
Provisionally accepted- 1 Guangxi Maternal and Child Health Hospital, Nanning, Guangxi Zhuang Region, China
- 2 Sheng Jing Hospital Affiliated, China Medical University, Shenyang, China
Background: Kindler Syndrome (KS, OMIM #173650), a rare autosomal recessive genetic disorder, is characterized by a spectrum of symptoms such as cutaneous fragility, blistering, photosensitivity, and mucosal involvement. These symptoms result from variations in the FERMT1 gene (Fermitin family member 1, OMIM: 607900), encoding kindlin-1, an essential component of focal adhesions.Objective: This study aims to ascertain the potential pathogenicity of a FERMT1 variant identified in a Chinese patient and to explore the phenotypic and molecular genetic characteristics of all reported cases of Kindler Syndrome in the Chinese population.Methods: Whole-exome sequencing (WES) was performed on the patient to identify candidate variants associated with KS, and Sanger sequencing was utilized to authenticate their presence and origin. To further assess the potential impact of these genetic variants, we employed a variety of in silico prediction tools. Concurrently, a review of various databases was undertaken to ascertain and consolidate information regarding cases of KS in Chinese families.We identified a novel likely pathogenic frameshift variant in the FERMT1 gene, specifically c.567_579delTATATATGACCCC (p.Ile190Serfs*10). The clinical presentation of this patient aligns with the diagnostic criteria for KS. The literature review reveals that the core clinical features of KS reported in the Chinese population include skin abnormalities (100%), as well as hyperkeratosis of the palms and soles (91.70%). Other clinical phenotypes encompass nail abnormalities (77.78%), abnormalities of the fingers/toes (75.00%), oral damage (70.00%), eye abnormalities (57.14%), and constipation (50.00%). Conclusion: Our study enriches the genetic landscape of KS in the Chinese population and augments the understanding of phenotypic variability resulting from FERMT1 gene variants. The findings hold considerable significance for refining variant-based screening, genetic diagnosis, and comprehending the molecular pathogenesis underlying FERMT1-related disorders.
Keywords: Kindler syndrome, FERMT1 gene, Novel variation, whole exome sequencing, genetic analysis
Received: 29 Apr 2024; Accepted: 28 Aug 2024.
Copyright: © 2024 Zhang, Yang, Shen, Wang and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fei Shen, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi Zhuang Region, China
LIN L. Wang, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi Zhuang Region, China
Jing s. Luo, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi Zhuang Region, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.