title: An autosomal-recessive form of cutis laxa is due to homozygous elastin mutations, and the phenotype may be modified by a heterozygous fibulin 5 polymorphism.
abstract: Cutis laxa (CL) is a heterogeneous group of connective tissue disorders characterized by loose, sagging skin and variable involvement of other organs. Autosomal-dominant forms are relatively mild, and may be caused by mutations in the elastin gene, whereas the more severe recessive forms have been associated with mutations in the fibulin 4 and fibulin 5 genes, as well as in a vesicular ATPase subunit. We describe here a previously unreported autosomal-recessive form of CL caused by homozygous recessive mutations in exon 12 of the elastin gene (p.P211S) in three patients from two related consanguineous Syrian families. Furthermore, we found that the presence of a polymorphism in the fibulin 5 gene in one of the patients seems to modify the phenotype, producing more severe symptoms. This polymorphism (p.L301M) was associated with mild symptoms in the mother of the patient, who was heterozygous for both the elastin and fibulin 5 mutations. To our knowledge, autosomal-recessive CL owing to homozygous mutations in the elastin gene has not been reported previously.
authors.affiliation: Department of Dermatology, Balamand University, Saint Georges Hospital, Beirut, Lebanon.
authors.forename: Hala
authors.initials: H
authors.lastname: Mégarbané
authors.forename: Jobard
authors.initials: J
authors.lastname: Florence
authors.forename: Jörn Oliver
authors.initials: JO
authors.lastname: Sass
authors.forename: Susanne
authors.initials: S
authors.lastname: Schwonbeck
authors.forename: Mario
authors.initials: M
authors.lastname: Foglio
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Susan
authors.initials: S
authors.lastname: Cure
authors.forename: Safa
authors.initials: S
authors.lastname: Saker
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
mesh_terms: D002648:Child; D002675:Child, Preschool; D003483:Cutis Laxa / Q000235:genetics* / Q000473:pathology; D004549:Elastin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D006031:Glycosylation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000097:blood; D013593:Syria; D014168:Transferrin / Q000031:analogs & derivatives
chemical_list: D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D012795:Sialoglycoproteins; D014168:Transferrin; C519074:sialotransferrin, human; D004549:Elastin