SLC29A3
solute carrier family 29 (nucleoside transporters), member 3; ENT3, FLJ11160
Nucleoside transporters, such as SLC29A3, mediate uptake of precursors for nucleotide synthesis by salvage pathways. They are also required for uptake of hydrophilic anticancer and antiviral nucleoside drugs.
Recent findings of biallelic mutations in SLC29A3 in 2 families reported to have familial RDD and in a kindred with Faisalabad histiocytosis (MIM.602782), which is an autosomal inherited form of histiocytosis with similarities to RDD, can explain the RDD-like immunophenotype.
Pathology
Germline mutations in H syndrome (MIM.612391)
- pigmented hypertrichosis
- insulin-dependent diabetes mellitus
- Rosai-Dorfman syndrome (#21178579#)
- H syndrome (MIM.612391) is a recently described autosomal recessive genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin and systemic manifestations including hepatosplenomegaly, cardiac anomalies, hearing loss, hypogonadism, low height, hypertriglyceridemia, hallux valgus, and flexion contractures.
- H syndrome results from mutations in the SLC29A3 gene, which encodes the human equilibrative nucleoside transporter hENT3.
- The cutaneous histopathology is characterized by a striking mononuclear cell infiltrate in the dermis consisting of CD68+ monocyte-derived cells and CD34+ and factor XIIIa+ dendrocytes.
germline mutations of SLC29A3 in:
- familial histiocytosis syndrome (Faisalabad histiocytosis)
- familial Rosai-Dorfman disease (Plos Genetics)
See also
adenosine-associated proteins (adenosine-associated genes)
References
A case of H syndrome showing immunophenotye similarities to Rosai-Dorfman disease. Avitan-Hersh E, Mandel H, Indelman M, Bar-Joseph G, Zlotogorski A, Bergman R. Am J Dermatopathol. 2011 Feb;33(1):47-51. PMID: #21178579#
Expanding the clinical spectrum of SLC29A3 gene defects. Spiegel R, Cliffe ST, Buckley MF, Crow YJ, Urquhart J, Horovitz Y, Tenenbaum-Rakover Y, Newman WG, Donnai D, Shalev SA. Eur J Med Genet. 2010 Sep-Oct;53(5):309-13. PMID: #20619369#
Early-onset sensorineural hearing loss is a prominent feature of H syndrome. Ramot Y, Sayama K, Sheffer R, Doviner V, Hiller N, Kaufmann-Yehezkely M, Zlotogorski A. Int J Pediatr Otorhinolaryngol. 2010 Jul;74(7):825-7. PMID: #20399510#
Mutations in the SLC29A3 gene are not a common cause of isolated autoantibody negative type 1 diabetes. Edghill EL, Hameed S, Verge CF, Rubio-Cabezas O, Argente J, Sumnik Z, Dusatkova P, Cliffe ST, Hennekam RC, Buckley MF, Hussain K, Ellard S, Attersley AT. JOP. 2009 Jul 6;10(4):457-8. PMID: 19581757
SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway. Cliffe ST, Kramer JM, Hussain K, Robben JH, de Jong EK, de Brouwer AP, Nibbeling E, Kamsteeg EJ, Wong M, Prendiville J, James C, Padidela R, Becknell C, van Bokhoven H, Deen PM, Hennekam RC, Lindeman R, Schenck A, Roscioli T, Buckley MF. Hum Mol Genet. 2009 Jun 15;18(12):2257-65. PMID: 19336477