Identification of a SLC19A2 nonsense mutation in Persian families with thiamine-responsive megaloblastic anemia

Abstract

Thiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive syndrome characterized by early-onset anemia, diabetes, and hearing loss caused by mutations in the SLC19A2 gene. We studied the genetic cause and clinical features of this condition in patients from the Persian population. A clinical and molecular investigation was performed in four patients from three families and their healthy family members. All had the typical diagnostic criteria. The onset of hearing loss in three patients was at birth and one patient also had a stroke and seizure disorder. Thiamine treatment effectively corrected the anemia in all of our patients but did not prevent hearing loss. Diabetes was improved in one patient who presented at the age of 8 months with anemia and diabetes after 2 months of starting thiamine. The coding regions of SLC19A2 were sequenced in all patients. The identified mutation was tested in all members of the families. Molecular analyses identified a homozygous nonsense mutation c.697C > T (p.Gln233*) as the cause of the disease in all families. This mutation was previously reported in a Turkish patient with TRMA and is likely to be a founder mutation in the Persian population.

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

“…To date, more than 40 different SLC19A2 mutations have been identified in less than 60 families [18][19][20][21][22][23]. The majority of these have been described in individual case reports or small series and the focus has been mainly on the haematological manifestations of the condition.…”

Loss-of-Function Mutation in Thiamine Transporter 1 in a Family With Autosomal Dominant Diabetes

“…SLC19A2 encodes thiamine transporter 1 (THTR1), a transmembrane protein that facilitates the transport of thiamine by shielding its positive charge from the repulsive force of the membrane. Homozygous SLC19A2 mutations have been described as the cause of thiamine-responsive megaloblastic anemia (TRMA) (Online Mendelian Inheritance in Man [OMIM] #249270), a syndrome characterized by megaloblastic anemia, diabetes, sensorineural deafness (1), and the variable combination of other neurological, cardiovascular, and neuroendocrine abnormalities such as optic atrophy (2), arrhythmia, heart defects (3,4), thyroid function alterations (5), and seizures (6).…”

A Case of Early-Onset Thiamine-Responsive Megaloblastic Anemia Syndrome

“…6 Sağırlığın nedeni net olarak bilinememektedir. Ancak, hayvan modellerinde kohleanın histopatolojik incelemesinde içteki tüysü hücrelerde dejenerasyon saptanmıştır.…”