2026-04-13T06:50:32Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/138912025-10-24T08:51:04Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097
RECERCAT
author
Douiev, Liza
author
Frank, Marika
author
Hanington, Lucy
author
Hoffman, Trevor
author
Irons, Mira B.
author
FERNANDEZ ALVAREZ, PAULA
author
Lasa-Aranzasti, Amaia
2025-10-24T08:51:04Z
2025-10-24T08:51:04Z
2025-10-20T11:46:16Z2025-10-20T11:46:16Z2025-08
http://hdl.handle.net/11351/13891
Exome sequencing; Loss‐of‐function; Phenotypic expansionSecuenciación del exoma; Pérdida de función; Expansión fenotípicaSeqüenciació de l'exoma; Pèrdua de funció; Expansió fenotípicaSIAH1 encodes for a RING-type E3 ubiquitin ligase involved in protein ubiquitination. More specifically, it positively regulates Wnt signaling through promoting the accumulation of β-catenin and mediates ubiquitination and degradation of Akt3 in neural development. Heterozygous de novo missense pathogenic variants in SIAH1 have been described in five unrelated individuals and are associated with developmental delay, hypotonia, and dysmorphic features. In this report, we present additional individuals from eight unrelated families and their clinical and genetic findings. We identified two missense and six predicted loss-of-function variants. Motor and speech delay and intellectual disabilities of varying severity were observed in all individuals. Neurodevelopmental issues, as well as infantile hypotonia and facial dysmorphism, were observed in the majority of individuals. Hearing loss, gastroesophageal reflux disease or other gastrointestinal issues, endocrinology abnormalities, and recurrent infections were observed in over 50% of individuals. This study expands the phenotypic spectrum of this syndrome and emphasizes the diverse impact of SIAH1 variation on multi-system clinical manifestations.
Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess
Discapacitat intel·lectual - Aspectes genètics
Fenotip
Trastorns del desenvolupament - Aspectes genètics
Anomalies cromosòmiques
PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype
CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Ligases::Ubiquitin-Protein Ligase Complexes::Ubiquitin-Protein Ligases
PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Neurodevelopmental Disorders::Developmental Disabilities
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Loss of Function Mutation
DISEASES::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability
FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo
COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::ligasas::complejos ubicuitina-proteína ligasa::ubicuitina-proteína ligasas
PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos del desarrollo neurológico::discapacidades del desarrollo
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación con pérdida de función
ENFERMEDADES::enfermedades del sistema nervioso::manifestaciones neurológicas::manifestaciones neuroconductuales::discapacidad intelectual
Expanding the SIAH1-Associated Phenotypic Spectrum: Insights From Loss-of-Function Variants
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion