Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000197740 | SCV000250060 | pathogenic | not provided | 2015-04-14 | criteria provided, single submitter | clinical testing | The c.1928_1952del25 mutation in the ELN gene, denoted as c.2114_2138del25 due to a difference in nomenclature, has been previously published in association with cutis laxa and aortic aneurysm (Szabo et al., 2006). The c.1928_1952del25 mutation causes a frameshift starting with codon Glycine 643, changes this amino acid to a Glutamic Acid residue and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Gly643GlufsX36. Expression studies have shown that the c.2114_2138del25 (c.1928_1952del25) mutation creates either a truncated protein product with a premature termination codon in exon 32 or an extended product lacking the sequence encoded by exon 32 as a result of normal alternative splicing but containing exons 30, 31, 33, 34 and part of the 3'-untranslated region of ELN (Szabo et al., 2006). Transgenic mice created using the elongated transcript were found to have severe respiratory distress, emphysema, abnormal lung mechanics, smaller size and higher mortality rate (Hu et al., 2010). Additionally, markers for TGF-beta signalling and the unfolded protein response were elevated and an increase in apoptosis was observed in the lungs of the mutant mice (Hu et al., 2010). Other frameshift mutations and gross deletions in the ELN gene have been reported in association with supravalvular aortic stenosis and cutis laxa. This variant was found in ELN |