Phenotypic Expansion of Autosomal Dominant LZTR1 -Related Disorders with Special Emphasis on Adult-Onset Features.

Autor:	Uliana V; Medical Genetics, University Hospital of Parma, 43126 Parma, Italy., Ambrosini E; Medical Genetics, University Hospital of Parma, 43126 Parma, Italy., Taiani A; Medical Genetics, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy., Cesarini S; Medical Genetics, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy., Cannizzaro IR; Medical Genetics, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy., Negrotti A; Neurology Unit, University Hospital of Parma, 43126 Parma, Italy., Serra W; Unit of Cardiology, University Hospital of Parma, 43126 Parma, Italy., Quintavalle G; Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, 43126 Parma, Italy., Micale L; Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Cappuccini snc, San Giovanni Rotondo, 71013 Foggia, Italy., Fusco C; Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Cappuccini snc, San Giovanni Rotondo, 71013 Foggia, Italy., Castori M; Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Cappuccini snc, San Giovanni Rotondo, 71013 Foggia, Italy., Martorana D; Medical Genetics, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy., Bortesi B; Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy., Belli L; Neurosurgery Unit, Head and Neck Department, University Hospital of Parma, 43126 Parma, Italy., Percesepe A; Medical Genetics, University Hospital of Parma, 43126 Parma, Italy.; Medical Genetics, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy., Pisani F; Child Neurology and Psychiatry Unit, Department of Human Neuroscience, Sapienza University, Via dei Sabelli 108, 00185 Rome, Italy., Barili V; Medical Genetics, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2024 Jul 13; Vol. 15 (7). Date of Electronic Publication: 2024 Jul 13.
DOI:	10.3390/genes15070916
Abstrakt:	Leucine zipper-like transcription regulator 1 (LZTR1) acts as a negative factor that suppresses RAS function and MAPK signaling; mutations in this protein may dysregulate RAS ubiquitination and lead to impaired degradation of RAS superfamily proteins. Germline LZTR1 variants are reported in Noonan syndrome, either autosomal dominant or autosomal recessive, and in susceptibility to schwannomatosis. This article explores the genetic and phenotypic diversity of the autosomal dominant LZTR1 -related disorders, compiling a cohort of previously published patients (51 with the Noonan phenotype and 123 with schwannomatosis) and presenting two additional adult-onset cases: a male with schwannomatosis and Parkinson's disease and a female with Noonan syndrome, generalized joint hypermobility, and breast cancer. This review confirms that autosomal dominant LZTR1 -related disorders exhibit an extreme phenotypic variability, ranging from relatively mild manifestations to severe and multi-systemic involvement, and offers updated frequences of each clinical feature. The aim is to precisely define the clinical spectrum of LZTR1 -related diseases, using also two new emblematic clinical cases. Gaining insight into the mechanisms underneath this variability is crucial to achieve precision diagnostics and the development of therapeutic interventions.
Databáze:	MEDLINE
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