Expanding the clinical spectrum of SLC29A3 gene defects.
H syndrome and pigmented hypertrichosis with insulin dependent diabetes (PHID) are allelic autosomal recessive syndromes reported in the last year to be caused by mutations in the SLC29A3 gene, which encodes the equilibrative nucleoside transporter hENT3. Herein, we report three new patients from a single family who present with phenotypes that associate features of both PHID and H syndrome. Genetic analysis of the SLC29A3 gene revealed that two affected sisters are compound heterozygotes for the previously reported mutations p.G427S and p.G437R, while their nephew was homozygous for the p.G437R mutation. In addition to this intra-familial genetic heterogeneity, these patients demonstrate considerable phenotypic variability. One sister had clinical features consistent with classical PHID phenotype, while her nephew's features were in keeping with the diagnosis of H syndrome. The second sister displayed the most severe phenotype which combined diagnostic features from both syndromes. This patient also had features not described previously, including severe seronegative polyarthritis involving large and small joints, and hypogonadotropic hypogonadism. These manifestations may be additional characteristics of the growing clinical spectrum of SLC29A3 defects. This report emphasizes the complex genotype phenotype correlation in SLC29A3 disorders and suggests that other factors are relevant to disease manifestations and severity.
Spiegel
Ronen
R
Genetic Institute, Ha'Emek Medical Center, Afula, Israel. spiegelr@zahav.net.il
Cliffe
Simon T
ST
Buckley
Michael F
MF
Crow
Yanick J
YJ
Urquhart
Jill
J
Horovitz
Yoseph
Y
Tenenbaum-Rakover
Yardena
Y
Newman
William G
WG
Donnai
Dian
D
Shalev
Stavit A
SA
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D030342:Genetic Diseases, Inborn; D006579:Heterozygote; D006801:Humans; D017495:Hyperpigmentation / Q000235:genetics; D006983:Hypertrichosis / Q000235:genetics; D008297:Male; D009154:Mutation; D033703:Nucleoside Transport Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome; D055815:Young Adult
D033703:Nucleoside Transport Proteins; C501424:SLC29A3 protein, human