Arina Puzriakova Added comment: Comment on list classification: Updating rating from Red to Green to match the rating on the GMS Thoracic aortic aneurysm and dissection (v1.2) panel.
Arina Puzriakova Phenotypes for gene: FBLN5 were changed from to ?Cutis laxa, autosomal dominant 2, OMIM:614434; Cutis laxa, autosomal recessive, type IA, OMIM:219100
Rebecca Whittington commented on gene: FBLN5: 614434/219100 AD/AR Cutis Laxa - cardiac phenotype includes ascending aortic aneurysm, vascular tortuosity and SVAS. Most HGMD variants (10) are associated with age-related macular degeneration, but 7 variants reported in association with cutis laxa
Rebecca Whittington commented on gene: FBLN5: Callewaert et al 2013 Hum Mutat 34:111 PMID:22829427 describe one missense and one nonsense variant c.649T>C p.Cys217Arg; c.1171G>T p.Glu391X (both homozygous in consanguineous families) but do not report segregation or functional analysis for either variant, but both had significant family history; p.Cys217Arg has previously been reported elsewhere. Hu et al 2006 Hum Mol Genet 15:3379 PMID:17035250 carried out functional analysis on two missense variants including Cys217Arg and have shown fibulin-5 is absent in skin from a homozygous p.ser227Pro patient with resulting disorganisation of elastic fibres. Loeys et al 2002 11:2113 PMID:12189163 characterised the Ser224Pro variant in 4 homozygous affected members of a large consangineous family - segregation data.
Rebecca Whittington reviewed gene: FBLN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal