Novel variant in LRP6 associated with unusual and severe clinical presentation: Case report - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Clinical Genetics Année : 2024

Novel variant in LRP6 associated with unusual and severe clinical presentation: Case report

OKT4 positive Hodgkin's disease.

Résumé

Low‐density lipoprotein receptor‐related protein 6 ( LRP6 ) is a co‐receptor of the Wnt signaling pathway, which plays an essential role in various biological activities during embryonic and postnatal development. LRP6 is exceptionally associated with rare diseases and always with autosomal dominant inheritance. Here we report a familial phenotype of high bone mass associated with skeletal anomalies and oligodontia but also persistent left superior vena cava, inguinal hernia, hepatic cysts, abnormal posterior fossa and genital malformations. Molecular analysis revealed a novel heterozygous variant, NM_002336.2: c.724T>C, p.(Trp242Arg), in affected individuals. This variant is located in the first β‐propellant motif of LRP6 , to which sclerostin ( SOST ) and dickkopf1 ( DKK1 ), two LRP6 co‐receptor inhibitors and various Wnt ligands bind. According to the literature and integrating data from structural analysis, this variant distorts the binding of SOST and DKK1 , thus leading to overactivation of Wnt signaling pathways involved in osteoblast differentiation. This novel heterozygous variant in LRP6 underlies the role of LRP6 in skeletal and dental disorders as well as, probably, cardiac, cerebral and genital developments.
Fichier principal
Vignette du fichier
Clinical Genetics - 2024 - Previdi - Novel variant in LRP6 associated with unusual and severe clinical presentation Case.pdf (826.79 Ko) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence

Dates et versions

hal-04600860 , version 1 (04-06-2024)

Licence

Identifiants

Citer

Anaïk Previdi, Christèle Dubourg, Valérie Cormier Daire, Mélanie Fradin, Corinne Collet. Novel variant in LRP6 associated with unusual and severe clinical presentation: Case report. Clinical Genetics, 2024, 105 (6), pp.666-670. ⟨10.1111/cge.14501⟩. ⟨hal-04600860⟩

Collections

INSERM UP-SANTE
2 Consultations
2 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More