title: 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 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.
authors: Growth & Development Research Centre, University of Tehran, Medical Sciences, Tehran, Iran.
authors: Aria
authors: A
authors: Setoodeh
authors: Amirreza
authors: A
authors: Haghighi
authors: Nasrollah
authors: N
authors: Saleh-Gohari
authors: Sian
authors: S
authors: Ellard
authors: Alireza
authors: A
authors: Haghighi
mesh_terms: D000749:Anemia, Megaloblastic / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D023281:Genomics / Q000379:methods; D034381:Hearing Loss / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007492:Iran; D007655:Ketoglutarate Dehydrogenase Complex / Q000172:deficiency / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013831:Thiamine / Q000627:therapeutic use; D013832:Thiamine Deficiency / Q000151:congenital; D044465:White People / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; D007655:Ketoglutarate Dehydrogenase Complex; D013831:Thiamine