This report describes Ehlers-Danlos syndrome, spondylodysplastic type 3 (EDSSPD3); EDSSPD3 exhibits autosomal recessive inheritance. The human gene implicated in this disease is solute carrier family 39 member 13 (SLC39A13), which encodes a transmembrane protein that is postulated to function as a zinc transporter. There is a single orthologous gene in Drosophila, Zip99C, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.
A UAS construct of the wild-type human Hsap\SLC39A13 gene has been introduced into flies; partial heterologous rescue (functional complementation) has been demonstrated.
Ubiquitous knockdown of Dmel\Zip99C effected by RNAi results developmental arrest in the pupal stage that can be rescued by iron supplementation, but not zinc. This work in flies supports the function of Zip99C as an iron transporter and suggests that impaired iron transport may play a role in this form of Ehlers-Danlos syndrome.
[updated Aug. 2018 by FlyBase; FBrf0222196]
Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications. [Genetics Home Reference, Ehlers-Danlos syndrome; 2020.08.25]
The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility. The main features of classic Ehlers-Danlos syndrome are loose-jointedness and fragile, easily bruised skin that heals with peculiar 'cigarette-paper' scars (Beighton, 1993). The current OMIM classification of Ehlers-Danlos syndromes is based on a 2017 international classification described by Malfait et al., 2017; pubmed:28306229), which recognizes 13 EDS subtypes. [from MIM:130000; 2020.08.25]
[EHLERS-DANLOS SYNDROME, SPONDYLODYSPLASTIC TYPE, 3; EDSSPD3](https://omim.org/entry/612350)
[SOLUTE CARRIER FAMILY 39 (ZINC TRANSPORTER), MEMBER 13; SLC39A13](https://omim.org/entry/608735)
The classic phenotypes of Ehlers-Danlos syndrome include joint laxity, skin hyperextensibility, and poor wound healing. [from MIM:130070; 2018.08.16]
Ehlers-Danlos syndrome spondylodysplastic type 3 is characterized by short stature, hyperelastic skin and hypermobile joints, protuberant eyes with bluish sclerae, finely wrinkled palms, and characteristic radiologic features (Giunta et al., 2008; pubmed:18513683). [from MIM:612350; 2018.08.16]
Ehlers-Danlos syndrome spondylodysplastic type 3 (EDSSPD3) is caused by homozygous mutation in the SLC39A13 gene. [from MIM:612350; 2018.08.16]
SLC39A13 which encodes a transmembrane protein that functions as a zinc transporter. [Gene Cards, SLC39A13; 2018.08.16]
SLC39A13 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003; pubmed:12659941). [from MIM:608735; 2018.08.16]
For this disease (EDSSPD3), an increased lysyl pyridinoline/hydroxylysyl pyridinoline (LP/HP) ratio, indicating underhydroxylation of collagen, is observed in tested patients. [from MIM:612350; 2018.08.16]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human SLC39A13 (1 Drosophila to 1 human). Dmel\Zip99C shares 46% identity and 60% similarity with the human gene.
