Expanding the clinical spectrum of SLC29A3 gene defects

Skin-Dominant Phenotype in a Patient with H Syndrome: Identification of a Novel Mutation in the <b><i>SLC29A3</i></b> Gene

“…Most of the patients with p.Glu444Ter or p.Thr449Arg mutations were classified as pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome or sinus histiocytosis with massive lymphadenopathy rather than H syndrome [Jonard et al, 2012], whereas p.Gly437Arg is 1 of the 2 most common mutations (G437R and G427S) described in H syndrome [Molho-Pessach et al, 2008b]. In our patient, neither endocrine involvement nor hearing loss were observed, but it is known that the disease spectrum ranges widely, and none of the features are specifically associated with a particular type of mutation [Spiegel et al, 2010;Jonard et al, 2012;Molho-Pessach et al, 2014].…”

“…Acute phase reactants were above normal limits. Increased inflammation markers (erythrocyte sedimentation rate and C-reactive protein levels) were reported previously in H syndrome patients in the literature [Spiegel et al, 2010;Shankarappa et al, 2011;Mohanan et al, 2013;Mutlu et al, 2013]. It would be useful to investigate clues of inflammation in cases with H syndrome in order to develop treatment strategies.…”

The histopathology and phenotypic variability in H syndrome

“…Phenotypic variability in H syndrome further emphasizes the need for diagnostic measures. The c.G1309>A mutation has been associated with multiple abnormalities including short stature, exophthalmos, dilated lateral scleral vasculature, hearing loss, congenital cardiac anomalies, hepatomegaly, hypogonadism, varicose veins, fixed flexion, hallux valgus, flat foot, malabsorption, and hyperglycemia 1, 6, 7, 8, 9, 10, 11, 12. Our patient had only hearing loss, a prominent feature of this syndrome 8.…”

Nucleoside Transporters (SLC28 and SLC29) Family

“…This is because SLC29A3 is the only nucleoside transporter studied to date that has been associated with inherited human diseases. Several syndromes, including the H syndrome (Molho-Pessach et al, 2008) and the Pigmented Hypertrichosis with Insulin dependent Diabetes (PHID) syndrome (Spiegel et al, 2010) have been associated with mutations in the SLC29A3 gene. The broad spectrum of clinical defects caused by SLC29A3 mutations may reflect the apparently complex biology of this transporter.…”

“…Turning to SLC29A3, it appears that genetic changes may be very important when seeking to understand the etiology of a variety of syndromes with which such changes have recently been associated. The relevant clinical conditions include H syndrome (Molho-Pessach et al, 2008) and the PHID syndrome (Spiegel et al, 2010). SLC29A3 variation affects hENT3-related biological functions.…”