Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.

Autor:	Alstrup M; Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: MOCHHA@rm.dk., Cesca F; Department of Life Sciences, University of Trieste, Trieste, Italy; IIT Center for Synaptic Neuroscience and Technology, Genova, Italy. Electronic address: fcesca@units.it., Krawczun-Rygmaczewska A; Department of Life Sciences, University of Trieste, Trieste, Italy; IIT Center for Synaptic Neuroscience and Technology, Genova, Italy., López-Menéndez C; Instituto de Investigaciones Biomédicas Sols-Morreale. Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III. Madrid, Spain., Pose-Utrilla J; Instituto de Investigaciones Biomédicas Sols-Morreale. Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III. Madrid, Spain., Castberg FC; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Pediatrics, North Zealand Hospital, Hilleroed, Denmark., Bjerager MO; Department of Pediatrics, North Zealand Hospital, Hilleroed, Denmark., Finnila C; Hudson Alpha Institute for Biotechnology, Huntsville, AL., Kruer MC; Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ; Departments of Child Health, Neurology, and Cellular & Molecular Medicine, and Program in Genetics, University of Arizona College of Medicine-Phoenix, Phoenix, AZ., Bakhtiari S; Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ; Departments of Child Health, Neurology, and Cellular & Molecular Medicine, and Program in Genetics, University of Arizona College of Medicine-Phoenix, Phoenix, AZ., Padilla-Lopez S; Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ; Departments of Child Health, Neurology, and Cellular & Molecular Medicine, and Program in Genetics, University of Arizona College of Medicine-Phoenix, Phoenix, AZ., Manwaring L; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO., Keren B; Département de génétique, AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France., Afenjar A; APHP. Sorbonne Université, Centre de Référence Malformations et maladies congénitales du cervelet et déficiences intellectuelles de causes rares, UF de génétique clinique, Hôpital Trousseau, Paris, France., Galatolo D; Molecular Medicine and Neurogenetics, IRCCS Stella Maris Foundation, Calambrone, Pisa, Italy., Scalise R; Molecular Medicine and Neurogenetics, IRCCS Stella Maris Foundation, Calambrone, Pisa, Italy., Santorelli FM; Molecular Medicine and Neurogenetics, IRCCS Stella Maris Foundation, Calambrone, Pisa, Italy., Shillington A; Department of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati, Cincinnati, OH., Vezain M; Univ Rouen Normandie, Inserm U1245, Normandie Univ, Rouen, France., Martinovic J; Department of Fetal Pathology, AP-HP Antoine Beclere Hospital, University Paris Saclay, Clamart, France., Stevens C; Department of Pediatrics, University of Tennessee College of Medicine, Chattanooga, TN., Gowda VK; Department of Pediatric Neurology, Indira Gandhi institute of child health, Bangalore, India., Srinivasan VM; Department of Pediatric Neurology, Indira Gandhi institute of child health, Bangalore, India., Thiffault I; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, MO; University of Missouri Kansas City School of Medicine, Kansas City, MO; Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO., Pastinen T; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, MO; University of Missouri Kansas City School of Medicine, Kansas City, MO., Baranano K; Johns Hopkins University, The Johns Hopkins Hospital, Baltimore, MD., Lee A; Department of Pediatrics, Division of Genetics and Genomics, Washington University, Saint Louis, MO., Granadillo J; Department of Pediatrics, Division of Genetics and Genomics, Washington University, Saint Louis, MO., Glassford MR; Department of Pediatrics, Division of Genetics, Metabolism, and Genomic Medicine, University of Michigan, Ann Arbor, MI; Department of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH., Keegan CE; Department of Pediatrics, Division of Genetics, Metabolism, and Genomic Medicine, University of Michigan, Ann Arbor, MI., Matthews N; WVU Medicine Children's Hospital, Division of Genetics, Morgantown, WV., Saugier-Veber P; Univ Rouen Normandie, Inserm U1245, Normandie Univ, Rouen, France; CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, Rouen, France., Iglesias T; Instituto de Investigaciones Biomédicas Sols-Morreale. Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III. Madrid, Spain. Electronic address: tiglesias@iib.uam.es., Østergaard E; Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Jul 18; Vol. 26 (11), pp. 101219. Date of Electronic Publication: 2024 Jul 18.
DOI:	10.1016/j.gim.2024.101219
Abstrakt:	Purpose: Spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising 8 with SINO and 4 with an autosomal recessive condition attributed to biallelic KIDINS220 variants. Methods: In our international cohort, we have included 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed the clinical and molecular data of our cohort and previously reported individuals and, based on functional experiments, reached a better understanding of the pathogenesis behind the KIDINS220-related disease. Results: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. A total of 92% had their diagnosis within 3 years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact, and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted. Conclusion: Our study provides further insights into the clinical spectrum, etiology, and predicted functional impact of KIDINS220 variants. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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