Diagnosis of a patient with severe sensorineural hearing loss as the initial symptom caused by novel compound heterozygous variant in SLC19A2 gene

Yanan Shi; Junyang Li; Xiaoqin Chen; Niu Li; Sijie Yang; Youjin Li; Min Zhou

doi:10.1016/j.bjorl.2025.101581

Brazilian Journal of Otorhinolaryngology (Jul 2025)

Diagnosis of a patient with severe sensorineural hearing loss as the initial symptom caused by novel compound heterozygous variant in SLC19A2 gene

Yanan Shi,
Junyang Li,
Xiaoqin Chen,
Niu Li,
Sijie Yang,
Youjin Li,
Min Zhou

Affiliations

Yanan Shi: Shanghai Jiao Tong University, School of Medicine, Shanghai Children’s Medical Center, Hainan Branch, Department of Otolaryngology, Sanya, China
Junyang Li: Shanghai Jiao Tong University, School of Medicine, Shanghai Children’s Medical Center, Department of Otolaryngology, Shanghai, China
Xiaoqin Chen: Fujian Medical University, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fuzhou, China
Niu Li: Shanghai Jiao Tong University, School of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai, China
Sijie Yang: Shanghai Jiao Tong University, School of Medicine, Shanghai Children’s Medical Center, Department of Otolaryngology, Shanghai, China
Youjin Li: Shanghai Jiao Tong University, School of Medicine, Shanghai Children’s Medical Center, Hainan Branch, Department of Otolaryngology, Sanya, China; Shanghai Jiao Tong University, School of Medicine, Shanghai Children’s Medical Center, Department of Otolaryngology, Shanghai, China; Corresponding authors.
Min Zhou: Shanghai Jiao Tong University, School of Medicine, Shanghai Children’s Medical Center, Key Laboratory of Pediatric Hematology and Oncology of China Ministry of Health, Department of Hematology and Oncology, Shanghai, China; Shanghai Jiao Tong University, School of Medicine, Shanghai Children’s Medical Center, Hainan Branch, Department of Hematology and Oncology, Sanya, China; Corresponding authors.

DOI: https://doi.org/10.1016/j.bjorl.2025.101581
Journal volume & issue: Vol. 91, no. 4
p. 101581

Abstract

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Objective: Thiamine-Responsive Megaloblastic Anemia (TRMA) syndrome, caused by biallelic variants in the SLC19A2 gene, typically presents with a triad of megaloblastic anemia, diabetes mellitus, and sensorineural hearing loss. This study aims to determine the genetic etiology and clinical phenotype of a patient who presented with severe sensorineural hearing loss as the initial symptom, and to expand our understanding of the SLC19A2 variant spectrum. Methods: Proband-only whole-exome sequencing was performed to screen the candidate variants, which were subsequently validated by Sanger sequencing within the family. cDNA sequencing based on RT-PCR and TA cloning analysis was used to determine the effect of splicing variants on mRNA processing of SLC19A2 gene. Detailed clinical features were evaluated by a diagnostic hearing test, laboratory and imaging examination. Results: A 2-year-5-month-old Chinese girl was diagnosed with diabetes mellitus and severe sensorineural hearing loss, without abnormal hemoglobin. DNA sequencing revealed a novel compound heterozygous variant of c.808-1G > A and c.1228C > T (p.Gln410*) in the SLC19A2 gene. Both variants were previously unreported. The c.808-1G > A splicing variant is located in intron 2 of SLC19A2, and is predicted to cause exon 3 skipping. The cDNA experiment confirmed this biological event, further indicating that the splicing variant can cause amino acid frameshift alteration (p.Glu270Valfs*10) in SLC19A2. Conclusion: We report a patient with TRMA syndrome (without anemia) caused by a novel compound heterozygous variant in SLC19A2 gene. This study suggests that the possibility of TRMA syndrome should be considered when encountering patients with early-onset severe sensorineural hearing loss in clinical practice. Level of evidence: Level 4.

Published in Brazilian Journal of Otorhinolaryngology

ISSN: 1808-8694 (Print); 1808-8686 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Otorhinolaryngology
Website: https://www.journals.elsevier.com/brazilian-journal-of-otorhinolaryngology/

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