Skeletal abnormalities, pediatric-onset severe osteoporosis, and multiple fragility fractures in a patient with a novel CTNNB1 de novo variant
Olga Lesnyak,
Francesca Marini,
Polina Sokolnikova,
Margarita Sorokina,
Kseniya Sukhareva,
Irina Artamonova,
Vladimir Kenis,
Olga Tkach,
Anna Kostareva,
Maria Luisa Brandi
Affiliations
Olga Lesnyak
North Western State Medical University named after I.I. Mechnikov, 41, Kirochnaya Street, St. Petersburg 191015, Russian Federation; Clinical Rheumatological Hospital, # 25, 30, B.Pod'yacheskaya Street, St. Petersburg 190068, Russian Federation; Corresponding author at: 30, B.Pod'yacheskaya, St. Petersburg 190068, Russian Federation.
Francesca Marini
Fondazione FIRMO Onlus, Fondazione Italiana per la Ricerca sulle Malattie dell'Osso, Via San Gallo 123, Florence 50129, Italy
Polina Sokolnikova
Almazov National Medical Research Centre, 2, Akkuratova Street, St. Petersburg 197341, Russian Federation
Margarita Sorokina
Almazov National Medical Research Centre, 2, Akkuratova Street, St. Petersburg 197341, Russian Federation
Kseniya Sukhareva
Almazov National Medical Research Centre, 2, Akkuratova Street, St. Petersburg 197341, Russian Federation
Irina Artamonova
Almazov National Medical Research Centre, 2, Akkuratova Street, St. Petersburg 197341, Russian Federation
Vladimir Kenis
North Western State Medical University named after I.I. Mechnikov, 41, Kirochnaya Street, St. Petersburg 191015, Russian Federation; H.Turner National Medical Research Center for Children's Orthopedics and Trauma Surgery, 12, lit. a, Lakhtinskaya Street, St. Petersburg 197136, Russian Federation
Almazov National Medical Research Centre, 2, Akkuratova Street, St. Petersburg 197341, Russian Federation; Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet (KI), Solna, 17176 Stockholm, Sweden
Maria Luisa Brandi
Fondazione FIRMO Onlus, Fondazione Italiana per la Ricerca sulle Malattie dell'Osso, Via San Gallo 123, Florence 50129, Italy; Donatello Bone Clinic, Villa Donatello Hospital, Via Attilio Ragionieri 101, 50019, Sesto Fiorentino, Florence, Italy
We report a case of a patient with a de novo germline heterozygous truncating variant of CTNNB1 gene (c.2172del, p.Tyr724Ter) causing neurodevelopmental disorder with spastic diplegia and visual defects syndrome (NEDSDV) associated with a new clinical feature — severe pediatric-onset osteoporosis and multiple fractures. A functional effect of the identified variant was demonstrated using adipose-tissue derived primary mesenchymal stem cells, where we detected the alteration of CTNNB1mRNA and β-catenin protein levels using real-time PCR and Western blot analysis.
