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HBS1L deficiency causes retinal dystrophy in a child and in a mouse model associated with defective development of photoreceptor cells.
Luo, Shiyu; Alwattar, Bilal; Li, Qifei; Bora, Kiran; Blomfield, Alexandra K; Lin, Jasmine; Fulton, Anne; Chen, Jing; Agrawal, Pankaj B.
Affiliation
  • Luo S; Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine and Holtz Children's Hospital, Jackson Health System, Miami, FL 33136, USA.
  • Alwattar B; Division of Genetics and Genomics and The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Li Q; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Bora K; Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine and Holtz Children's Hospital, Jackson Health System, Miami, FL 33136, USA.
  • Blomfield AK; Division of Genetics and Genomics and The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Lin J; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Fulton A; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Chen J; Division of Genetics and Genomics and The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Agrawal PB; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Dis Model Mech ; 17(8)2024 Aug 01.
Article in En | MEDLINE | ID: mdl-38966981
ABSTRACT
Inherited retinal diseases encompass a genetically diverse group of conditions caused by variants in genes critical to retinal function, including handful of ribosome-associated genes. This study focuses on the HBS1L gene, which encodes for the HBS1-like translational GTPase that is crucial for ribosomal rescue. We have reported a female child carrying biallelic HBS1L variants, manifesting with poor growth and neurodevelopmental delay. Here, we describe the ophthalmologic findings in the patient and in Hbs1ltm1a/tm1a hypomorph mice and describe the associated microscopic and molecular perturbations. The patient has impaired visual function, showing dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses. Hbs1ltm1a/tm1a mice exhibited profound thinning of the entire retina, specifically of the outer photoreceptor layer, due to extensive photoreceptor cell apoptosis. Loss of Hbs1l resulted in comprehensive proteomic alterations by mass spectrometry analysis, with an increase in the levels of 169 proteins and a decrease in the levels of 480 proteins, including rhodopsin (Rho) and peripherin 2 (Prph2). Gene Ontology biological process and gene set enrichment analyses reveal that the downregulated proteins are primarily involved in phototransduction, cilium assembly and photoreceptor cell development. These findings underscore the importance of ribosomal rescue proteins in maintaining retinal health, particularly in photoreceptor cells.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Disease Models, Animal / Retinal Dystrophies Limits: Animals / Child / Female / Humans Language: En Journal: Dis Model Mech / Dis. model. mech. (Print) / Disease models & mechanisms (Online) Journal subject: MEDICINA Year: 2024 Document type: Article Affiliation country: United States Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Disease Models, Animal / Retinal Dystrophies Limits: Animals / Child / Female / Humans Language: En Journal: Dis Model Mech / Dis. model. mech. (Print) / Disease models & mechanisms (Online) Journal subject: MEDICINA Year: 2024 Document type: Article Affiliation country: United States Country of publication: United kingdom