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Mol Genet Genomic Med. 2019 Jul;7(7):e00777. doi: 10.1002/mgg3.777. Epub 2019 May 29.

Whole exome sequencing identifies a new mutation in the SLC19A2 gene leading to thiamine-responsive megaloblastic anemia in an Egyptian family.

Author information

1
Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
2
UMR8200-CNRS, Gustave Roussy, Villejuif Cedex, France.
3
Université Paris-Sud, Université Paris-Saclay, Orsay, France.
4
Equipe labellisée "La Ligue Contre le Cancer", Villejuif Cedex, France.

Abstract

BACKGROUND:

The Solute Carrier Family 19 Member 2 (SLC19A2, OMIM *603941) encodes the thiamine transporter 1 (THTR-1) that brings thiamine (Vitamin B1) into cells. THTR-1 is the only thiamine transporter expressed in bone marrow, cochlear, and pancreatic beta cells. THTR-1 loss-of-function leads to the rare recessive genetic disease Thiamine-Responsive Megaloblastic Anemia (TRMA, OMIM #249270).

METHODS:

In vitro stimulated blood lymphocytes were used for cytogenetics and the isolation of genomic DNA used to perform whole exome sequencing (WES). To validate identified mutations, direct Sanger sequencing was performed following PCR amplification.

RESULTS:

A 6-year-old male born from a consanguineous couple presenting bone marrow failure and microcephaly was referred to our clinic for disease diagnosis. The patient presented a normal karyotype and no chromosomal fragility in response to DNA damage. WES analysis led to the identification of a new pathogenic variant in the SLC19A2 gene (c.596C>G, pSer199Ter) allowing to identify the young boy as a TRMA patient.

CONCLUSION:

Our analysis extend the number of inactivating mutations in SLC19A2 leading to TRMA that could guide future prenatal diagnosis for the family and follow-up for patients.

KEYWORDS:

SLC19A2 ; THTR-1; bone marrow failure; deafness; diabetes; thiamine-responsive megaloblastic anemia

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