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Novel nonsense mutation (p.Ile411Metfs*12) in the SLC19A2 gene causing Thiamine Responsive Megaloblastic Anemia in an Indian patient.

Abstract
Thiamine-responsive megaloblastic anemia (TRMA), an autosomal recessive disorder, is caused by mutations in SLC19A2 gene encodes a high affinity thiamine transporter (THTR-1). The occurrence of TRMA is diagnosed by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Here, we report a female TRMA patient of Indian descent born to 4th degree consanguineous parents presented with retinitis pigmentosa and vision impairment, who had a novel homozygous mutation (c.1232delT/ter422; p.Ile411Metfs*12) in 5th exon of SLC19A2 gene that causes premature termination of hTHTR-1. PROSITE analysis predicted to abrogate GPCRs family-1 signature motif in the variant by this mutation c.1232delT/ter422, suggesting uncharacteristic rhodopsin function leading to cause RP clinically. Thiamine transport activity by the clinical variant was severely inhibited than wild-type THTR-1. Confocal imaging had shown that the variant p.I411Mfs*12 is targeted to the cell membrane and showed no discrepancy in membrane expression than wild-type. Our findings are the first report, to the best of our knowledge, on this novel nonsense mutation of hTHTR-1 causing TRMA in an Indian patient through functionally impaired thiamine transporter activity.
AuthorsParamasivam Manimaran, Veedamali S Subramanian, Sellamuthu Karthi, Krishnan Gandhimathi, Perumal Varalakshmi, Ramasamy Ganesh, Andiappan Rathinavel, Hamid M Said, Balasubramaniem Ashokkumar
JournalClinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 452 Pg. 44-9 (Jan 15 2016) ISSN: 1873-3492 [Electronic] Netherlands
PMID26549656 (Publication Type: Journal Article)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.

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