Monogenic hearing loss

Gene: SLC19A2

Green List (high evidence)

Comment on list classification: There are numerous patients reported with Thiamine-Responsive Megaloblastic Anemia (TRMA) syndrome, caused by biallelic variants in the SLC19A2 gene, which typically presents with a triad of megaloblastic anemia, diabetes mellitus, and sensorineural hearing loss. Hearing loss can be the main presenting feature. Hence, this gene should be promoted to Green for monogenic hearing loss, with MOI set to BIALLELIC, autosomal or pseudoautosomal.

Created: 27 Mar 2026, 11:40 a.m. | Last Modified: 27 Mar 2026, 11:40 a.m.

Panel Version: 5.61

PMID: 40220483 Shi et al., 2025
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. Study reported a 2-year-5-month-old Chinese girl diagnosed with diabetes mellitus and severe sensorineural hearing loss, without abnormal hemoglobin. Severe sensorineural hearing loss was the initial symptom. DNA sequencing revealed compound heterozygous variants c.808-1G>A, (p.Glu270Valfs*10) and c.1228C>T (p.Gln410*) in the SLC19A2 gene.

PMID: 38037112 Di Candia et al., 2023
Italian case series of 4 TRMA patients. All 4 harboured biallelic nonsense variants in SLC19A2. Thiamine therapy did not resolve the clinical manifestation of deafness.

PMID: 31095747 Marcé-Grau et al., 2019
Review article, stating at least 136 patients with TRMA and biallelic SLC19A2 variants have been reported, with hearing loss being a core phenotype of the syndrome.

Functional evidence: PMID: 11386850 Oishi et al., 2001 - KO slc19a2 -/- mice showed diabetes mellitus, sensorineural deafness and megaloblastosis.

Created: 27 Mar 2026, 11:37 a.m. | Last Modified: 27 Mar 2026, 11:37 a.m.

Panel Version: 5.57

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270

Publications

• 38037112
• 40220483

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#249270:Thiamine-responsive megaloblastic anemia syndrome[Short stature (in some patients); Sensorineural deafness; Optic atrophy (in some patients)Maculopathy (uncommon)Cone-rod dystrophy (uncommon)Retinal degeneration (in some patients)Visual loss (in some patients)Nystagmus (in some patients); Congenital heart defects (in some patients)Atrial septal defect (uncommon)Ventricular septal defect (in some patients)Conduction defects (in some patients)Arrhythmias (in some patients)Cardiomyopathy (uncommon); Situs inversus (uncommon); Gastroesophageal reflux (uncommon); Cryptorchidism (uncommon); Developmental delay (uncommon)Seizures (uncommon)Stroke (uncommon)Ataxia (uncommon); Diabetes mellitus; Megaloblastic anemiaSideroblastic anemiaThrombocytopenia; Serum thiamine is normal]

Publications

• PMID:10391221
• 10391222
• 10391223
• 10542220
• 10874303
• 10978358
• 12393806
• 12454006
• 14994241
• 16642288
• 19879271
• 21868632
• 9399900