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LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder.
Chettle, James; Louie, Raymond J; Larner, Olivia; Best, Robert; Chen, Kevin; Morris, Josephine; Dedeic, Zinaida; Childers, Anna; Rogers, R Curtis; DuPont, Barbara R; Skinner, Cindy; Küry, Sébastien; Uguen, Kevin; Planes, Marc; Monteil, Danielle; Li, Megan; Eliyahu, Aviva; Greenbaum, Lior; Mor, Nofar; Besnard, Thomas; Isidor, Bertrand; Cogné, Benjamin; Blesson, Alyssa; Comi, Anne; Wentzensen, Ingrid M; Vuocolo, Blake; Lalani, Seema R; Sierra, Roberta; Berry, Lori; Carter, Kent; Sanders, Stephan J; Blagden, Sarah P.
Afiliación
  • Chettle J; Department of Oncology, University of Oxford, Oxford, UK.
  • Louie RJ; Greenwood Genetic Center, Greenwood, SC, USA. Electronic address: rlouie@ggc.org.
  • Larner O; University of South Carolina School of Medicine Greenville, Greenville, SC, USA.
  • Best R; University of South Carolina School of Medicine Greenville, Greenville, SC, USA.
  • Chen K; Yale University, New Haven, CT, USA.
  • Morris J; Department of Oncology, University of Oxford, Oxford, UK.
  • Dedeic Z; Department of Oncology, University of Oxford, Oxford, UK.
  • Childers A; Greenwood Genetic Center, Greenwood, SC, USA.
  • Rogers RC; Greenwood Genetic Center, Greenwood, SC, USA.
  • DuPont BR; Greenwood Genetic Center, Greenwood, SC, USA.
  • Skinner C; Greenwood Genetic Center, Greenwood, SC, USA.
  • Küry S; Nantes Université, CHU Nantes, Service de Génétique Médicale, 44000 Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, L'institut du thorax, 44000 Nantes, France.
  • Uguen K; Service de Génétique Médicale et Biologie de la Reproduction, CHRU de Brest, Brest, France.
  • Planes M; Service de Génétique Médicale et Biologie de la Reproduction, CHRU de Brest, Brest, France.
  • Monteil D; Naval Medical Center Portsmouth, Portsmouth, VA, USA.
  • Li M; Invitae, San Francisco Corp., San Francisco, CA, USA.
  • Eliyahu A; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Greenbaum L; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel.
  • Mor N; The Genomic Unit, Sheba Cancer Research Centre, Sheba Medical Center, Tel Hashomer, Israel.
  • Besnard T; Nantes Université, CHU Nantes, Service de Génétique Médicale, 44000 Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, L'institut du thorax, 44000 Nantes, France.
  • Isidor B; Nantes Université, CHU Nantes, Service de Génétique Médicale, 44000 Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, L'institut du thorax, 44000 Nantes, France.
  • Cogné B; Nantes Université, CHU Nantes, Service de Génétique Médicale, 44000 Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, L'institut du thorax, 44000 Nantes, France.
  • Blesson A; Kennedy Krieger Institute, Baltimore, MD, USA.
  • Comi A; Kennedy Krieger Institute, Baltimore, MD, USA.
  • Wentzensen IM; GeneDx, Gaithersburg, MD, USA.
  • Vuocolo B; Baylor College of Medicine, Houston, TX, USA.
  • Lalani SR; Baylor College of Medicine, Houston, TX, USA.
  • Sierra R; Baylor College of Medicine, Houston, TX, USA.
  • Berry L; Baylor College of Medicine, Houston, TX, USA.
  • Carter K; University of Texas Rio Grande Valley, Edinburg, TX, USA.
  • Sanders SJ; Institute of Developmental and Regenerative Medicine, Department of Paediatrics, University of Oxford, Oxford, UK; Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Blagden SP; Department of Oncology, University of Oxford, Oxford, UK. Electronic address: sarah.blagden@oncology.ox.ac.uk.
HGG Adv ; 5(4): 100345, 2024 Aug 30.
Article en En | MEDLINE | ID: mdl-39182167
ABSTRACT
Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: HGG Adv Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: HGG Adv Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos