Severe Phenotype of Cutis Laxa Type 1B with Antenatal Signs due to a Novel Homozygous Nonsense Mutation in .

Date publication

juillet 2018

Journal

Molecular syndromology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr ALBUISSON Juliette

Tous les auteurs :
Letard P, Schepers D, Albuisson J, Bruneval P, Spaggiari E, Van de Beek G, Khung-Savatovsky S, Belarbi N, Capri Y, Delezoide AL, Loeys B, Guimiot F

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30140196

Résumé

mutations are known to be responsible for autosomal recessive cutis laxa type 1B (ARCL1B), a rare multisystem disease affecting skin, skeleton, and vascular structures. We report 2 additional related cases of ARCL1B of particular severity leading to termination of pregnancy. Cardinal signs of this connective tissue disease were already seen during the second trimester of pregnancy, then confirmed and clarified at autopsy. Anomalies included cutis laxa, arachnodactyly, clubfoot, wormian bones, moderate bowing of long bones with slender bone trabeculae, rib fractures, undermuscularized diaphragm, hiatal hernia, and arterial tortuosity with thick vascular walls and disorganized elastic fibers. Sequencing of the gene revealed a novel homozygous nonsense mutation: c.639C>A (p.Cys213*). We performed a thorough histological analysis and discuss differential diagnoses, genotype-phenotype correlations, and the challenge of prenatal diagnosis of this disease.

Mots clés

Arterial tortuosity, Autopsy, Autosomal recessive cutis laxa type 1B, Bone fractures, EFEMP2, Elastic tissue, FBLN4, Fetus, Fibulin-4, Prenatal diagnosis

Référence

Mol Syndromol. 2018 07;9(4):190-196