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

• Published in: Gene 2013-05, Vol.519 (2), p.295-297
• Main Authors: Setoodeh, Aria, Haghighi, Amirreza, Saleh-Gohari, Nasrollah, Ellard, Sian, Haghighi, Alireza
• Format: Article
• Language: English
• Subjects: anemia; Anemia, Megaloblastic; Anemia, Megaloblastic - diagnosis; Anemia, Megaloblastic - drug therapy; Anemia, Megaloblastic - genetics; Child; Child, Preschool; Codon, Nonsense; deficiency; diabetes; Diabetes Mellitus; Diabetes Mellitus - diagnosis; Diabetes Mellitus - drug therapy; Diabetes Mellitus - genetics; diagnosis; drug therapy; Female; genes; Genetic Association Studies; genetics; Genomics; Genomics - methods; hearing; Hearing Loss; Hearing Loss - diagnosis; Hearing Loss - drug therapy; Hearing Loss - genetics; Hearing Loss, Sensorineural; Hearing Loss, Sensorineural - diagnosis; Hearing Loss, Sensorineural - drug therapy; Hearing Loss, Sensorineural - genetics; homozygosity; Homozygote; Humans; Infant; Iran; Ketoglutarate Dehydrogenase Complex; Ketoglutarate Dehydrogenase Complex - deficiency; Ketoglutarate Dehydrogenase Complex - genetics; Male; Membrane Transport Proteins; Membrane Transport Proteins - genetics; methods; nonsense mutation; patients; Rogers syndrome; Sequence Analysis, DNA; SLC19A2; stroke; therapeutic use; thiamin; Thiamine; Thiamine - therapeutic use; Thiamine Deficiency - congenital; Thiamine-responsive megaloblastic anemia; TRMA; White People; White People - genetics
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2013.02.008

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 8months with anemia and diabetes after 2months 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. ► A non-sense SLC19A2 in four patients with TRMA indicating its high frequency in Persian population. ► Most patients with this mutation had short stature. ► This study expands the knowledge about the of genotype–phenotype correlations in TRMA. ► The results have implications for genetic counseling in other affected families.