Severe congenital cutis laxa: Identification of novel homozygous LOX gene variants in two families.
ARCL1 (autosomal recessive cutis laxa type 1)
LOX
Lysyl oxidase
cutis laxa
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
12
04
2021
received:
06
03
2021
accepted:
15
04
2021
pubmed:
19
4
2021
medline:
31
12
2021
entrez:
18
4
2021
Statut:
ppublish
Résumé
We report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy-textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity. Post-mortem examination in two of the babies further revealed widespread ectasia and tortuosity of medium and large sized arteries, myocardial hypertrophy, rib and skull fractures. The presence of fractures initially suggested a diagnosis of osteogenesis imperfecta. Under light microscopy bony matrices were abnormal and arterial wall architecture was grossly abnormal showing fragmented elastic fibres. Molecular analysis of known cutis laxa genes did not yield any pathogenic defects. Whole exome sequencing of DNA following informed consent identified two separate homozygous variants in the LOX (Lysyl Oxidase) gene. LOX belongs to the 5-lysyl oxidase gene family involved in initiation of cross-linking of elastin and collagen. A mouse model of a different variant in this gene recapitulates the phenotype seen in the three babies. Our findings suggest that the LOX gene is a novel cause of severe congenital cutis laxa with arterial tortuosity, bone fragility and respiratory failure.
Substances chimiques
LOX protein, human
EC 1.4.3.13
Protein-Lysine 6-Oxidase
EC 1.4.3.13
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
168-175Informations de copyright
© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.
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