Further Exploring the TRRAP Genotype–Phenotype Correlations: Report of Three New Patients With A Focus on Skeletal Anomalies
TRRAP encodes a multidomain pseudokinase involved in histone acetyltransferase complexes. TRRAP pathogenic variants were linked to neurodevelopmental disorders, intellectual disability, congenital anomalies, and hearing loss. We report on three unrelated patients with TRRAP missense variants. Patient #1, a girl with severe intellectual disability, autism features, and preaxial polydactyly, displays the c.5575C>T, p.(Arg1859Cys) variant. Patient #2, a boy with developmental delay and facial anomalies, harbors the c.5647G>A, p.(Gly1883Arg) variant. Patient #3, a girl with developmental delay, epilepsy, and renal artery stenosis, carries the c.8572C>T, p.(Arg2858Trp) variant. These new cases broaden the TRRAP phenotypic spectrum, updating genotype-phenotype correlations. Osteoclast differentiation in Patient #1 and TRRAP expression in osteoclasts and osteoblasts were analyzed, leading to the assumption of a role of TRRAP in bone remodeling and in the observed skeletal anomalies.
Authors
- Domenico Barbuti
- Antonio Novelli (ORCID: https://orcid.org/0000-0002-9037-4297)
- Maria Cristina Digilio (ORCID: https://orcid.org/0000-0002-0205-9634)
- Maria Rosaria Iascone (ORCID: https://orcid.org/0000-0002-4707-212X)
- Andrea Bartuli
- Lorenzo Sinibaldi (ORCID: https://orcid.org/0000-0002-1371-936X)
- Maria Lisa Dentici (ORCID: https://orcid.org/0000-0002-9505-5906)
- Chiara Minotti (ORCID: https://orcid.org/0000-0001-8616-5065)
- Sara Terreri (ORCID: https://orcid.org/0000-0002-5791-6306)
- Ludovico Graziani (ORCID: https://orcid.org/0000-0002-7217-7388)
- Daniela Longo (ORCID: https://orcid.org/0000-0002-0097-736X)
- Andrea Del Fattore (ORCID: https://orcid.org/0000-0003-3848-412X)
- Rosario Ruta (ORCID: https://orcid.org/0000-0002-0582-2017)
- Ugo Cavallari (ORCID: https://orcid.org/0000-0002-3395-4033)
- Laura Pezzoli (ORCID: https://orcid.org/0000-0002-8111-563X)
- Giuseppe Novelli (ORCID: https://orcid.org/0000-0002-7781-602X)
- Francesca Romana Lepri (ORCID: https://orcid.org/0000-0001-5331-0473)
- Michelina Armando
Institutions
- University of Rome Tor Vergata (IT)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Saint Camillus International University of Health and Medical Sciences (IT)
- Ospedale Papa Giovanni XXIII (IT)
- Bambino Gesù Children's Hospital (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Publication Details
- Journal
- Clinical Genetics
- Published
- 2025-06-29
- DOI
- https://doi.org/10.1111/cge.70013
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministero della Salute