3. Novel variant of the TGM1 gene in association with lamellar ichthyosis
Main Article Content
Abstract
Lamellar ichthyosis (LI) , the most common subtype of autosomal recessive congenital ichthyosis (ARCI), derives from homozygous and compound heterozygous mutations in the TGM1 gene. In this study, we report a compound homozygous variant in two siblings with lamellar ichthyosis, specifically c.167C>T and c.653G>T, identified through next-generation sequencing (NGS) and validated by Sanger sequencing. We then classified the variants according to the ACMG/AMP/Clingen SVI criteria and predicted their impact on protein function using multiple in-silico algorithms. The novel variant, c.653G>T was proven to be the cause of LI in the family. This study adds valuable data regarding TGM1 variants in the congenital ichthyosis population in Vietnam, providing a critical basis for diagnosis, genetic counseling, and patient management.
Article Details
Keywords
Ichthyosis, TGM1 gene, ARCI
References
2. Rajpopat S, Moss C, Mellerio J, et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Archives of dermatology. 2011; 147(6): 681-686.
3. Glick JB, Craiglow BG, Choate KA, et al. Improved management of harlequin ichthyosis with advances in neonatal intensive care. Pediatrics. 2017; 139(1).
4. Zeng J, Shan B, Guo L, Lv S, Li F. Compound Heterozygous Mutations in TGM1 Causing a Severe Form of Lamellar Ichthyosis: A Case Report. Pharmacogenomics and Personalized Medicine. 2022: 583-588.
5. Diociaiuti A, Corbeddu M, Rossi S, et al. Cross-sectional study on autosomal recessive congenital ichthyoses: association of genotype with disease severity, phenotypic, and ultrastructural features in 74 Italian patients. Dermatology. 2024; 240(3): 397-413.
6. Harrison SM, Biesecker LG, Rehm HL. Overview of specifications to the ACMG/AMP variant interpretation guidelines. Current protocols in human genetics. 2019; 103(1): e93.
7. Nguyễn Phương Mai, Đoàn Thị Kim Phượng, Nguyễn Thị Minh Ngọc, Hoàng Thị Ngọc Lan, Lương Thị Lan Anh. Bệnh Da vảy cá bẩm sinh di truyền lặn liên quan đến biến thể dị hợp tử phức trên gen TGm-1. Tạp chí Y học Việt Nam. 2023 Tập 528 (Tháng 7 - Số chuyên đề). 2023;159-167.
8. Farasat S, Wei M-H, Herman M, et al. Novel transglutaminase-1 mutations and genotype–phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA. Journal of medical genetics. 2009; 46(2): 103-111.
9. Gånemo A, Pigg M, Virtanen M, et al. Autosomal recessive congenital ichthyosis in Sweden and Estonia: clinical, genetic and ultrastructural findings in eighty-three patients. Acta dermato-venereologica. 2003; 83(1): 24-30.
10. Al-Naamani A, Al-Waily A, Al-Kindi M, Al-Awadi M, Al-Yahyaee SA. Transglutaminase-1 mutations in Omani families with lamellar ichthyosis. Medical Principles and Practice. 2013; 22(5): 438-443.
11. Pigg MH, Bygum A, Gånemo A, et al. Spectrum of autosomal recessive congenital ichthyosis in Scandinavia: clinical characteristics and novel and recurrent mutations in 132 patients. Acta dermato-venereologica. 2016; 96(7): 932-937.
12. Bourrat E, Blanchet-Bardon C, Derbois C, Cure S, Fischer J. Specific TGM1 mutation profiles in bathing suit and self-improving collodion ichthyoses: phenotypic and genotypic data from 9 patients with dynamic phenotypes of autosomal recessive congenital ichthyosis. Archives of dermatology. 2012; 148(10): 1191-1195.
13. Rodríguez-Pazos L, Ginarte M, Fachal L, Toribio J, Carracedo A, Vega A. Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects. British Journal of Dermatology. 2011; 165(4): 906-911.