2026-04-17T21:27:28Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/138912025-10-24T08:51:04Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

00925njm 22002777a 4500 dc Douiev, Liza author Frank, Marika author Hanington, Lucy author Hoffman, Trevor author Irons, Mira B. author FERNANDEZ ALVAREZ, PAULA author Lasa-Aranzasti, Amaia author 2025-10-20T11:46:16Z 2025-10-20T11:46:16Z 2025-08 Exome sequencing; Loss‐of‐function; Phenotypic expansion Secuenciación del exoma; Pérdida de función; Expansión fenotípica Seqüenciació de l'exoma; Pèrdua de funció; Expansió fenotípica SIAH1 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. http://hdl.handle.net/11351/13891 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