2026-04-13T02:00:08Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/135342025-10-24T10:37:29Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Durizot, Meghane
author
BURGLEN, Lydie
author
Garel, Catherine
author
Blondiaux, Eléonore
author
Riquet, Audrey
author
Floret, Valentine
author
Valenzuela, Irene
2025-10-24T10:37:29Z
2025-10-24T10:37:29Z
2025-08-18T08:39:50Z2025-08-18T08:39:50Z2025-09
http://hdl.handle.net/11351/13534
Attenuated phenotype; Neurodevelopmental disorder; TubulinopathiesFenotip atenuat; Trastorn del neurodesenvolupament; TubulinopatiesFenotipo atenuado; Trastorno del neurodesarrollo; TubulinopatíasBackground: Tubulinopathies are neurodevelopmental disorders caused by pathogenic variants in tubulin-encoding genes, typically presenting with intellectual disability (ID), epilepsy, motor impairments, and distinct brain malformations. While most cases are de novo and severe, recent reports suggest the existence of milder imaging and clinical phenotypes, including familial cases with attenuated symptoms.
Methods: Through international collaboration, clinical, imaging, and molecular data were collected from 24 individuals (≥4 years old) across 16 families with pathogenic or likely pathogenic variants in TUBA1A, TUBB2B, TUBB3, TUBB, or TUBB2A. Patients were selected based on absence of ID and availability of brain MRI. Genetic inheritance patterns and genotype–phenotype correlations were analyzed.
Results: Fifteen patients were identified through fetal or pediatric imaging and nine through familial investigations. No cases exhibited severe cortical gyration anomalies. TUBB3 was the most frequently mutated gene (12/24, 50%), and 7 out of 14 total variants were inherited. Two recurrent variants, TUBB3 p.(Pro357Leu) and TUBB p.(Asn52Ser), were associated with non-ID phenotypes in both the current cohort and literature.
Conclusions: This study broadens the spectrum of tubulinopathies to include mild imaging phenotypes with attenuated clinical features in children and adults. Absence of major cortical malformations, inherited mutations, and specific genetic variants may serve as favorable prognostic markers. These findings have important implications for genetic counseling, particularly in prenatal cases.
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Trastorns del desenvolupament - Aspectes genètics
Fenotip
Tubulines
Discapacitat intel·lectual - Aspectes genètics
PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype
PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Neurodevelopmental Disorders
Other subheadings::Other subheadings::Other subheadings::/genetics
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins::Tubulin
DISEASES::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability
FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo
PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos del desarrollo neurológico
Otros calificadores::Otros calificadores::Otros calificadores::/genética
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::aminoácidos, péptidos y proteínas::proteínas::proteínas del tejido nervioso::tubulina (proteína)
ENFERMEDADES::enfermedades del sistema nervioso::manifestaciones neurológicas::manifestaciones neuroconductuales::discapacidad intelectual
Attenuated Clinical Forms of Tubulinopathies in Children and Adults: A Series of 24 Individuals
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion