Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss
American Journal of Human Genetics, Volume 108, No. 10, Year 2021
Notification
URL copied to clipboard!
Description
Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype. © 2021
Authors & Co-Authors
Bakhtiari, Somayeh
United States, Phoenix
Barrow Neurological Institute
United States, Phoenix
University of Arizona College of Medicine – Phoenix
Kaiyrzhanov, Rauan
United Kingdom, London
University College London
Wagner, Matias
Germany, Munich
Tum Fakultät Für Medizin
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Pagnozzi, Alex M.
Australia, Canberra
Commonwealth Scientific and Industrial Research Organisation
Webster, Richard I.
Australia, Sydney
The Children's Hospital at Westmead
Worgan, Lisa C.
Australia, Sydney
Royal Prince Alfred Hospital
Håkonarson, Håkon H.
United States, Philadelphia
The Children's Hospital of Philadelphia
Guo, Y.
United States, Philadelphia
The Children's Hospital of Philadelphia
Jain, Mahim
United States, Baltimore
Kennedy Krieger Institute
Rodan, Lance Harrington
United States, Boston
Boston Children's Hospital
Abbott, Mary Alice
United States, Springfield
Baystate Children's Hospital
Cohen, Julie S.
United States, Baltimore
Kennedy Krieger Institute
United States, Baltimore
Johns Hopkins School of Medicine
Alhaddad, Bader
Germany, Munich
Tum Fakultät Für Medizin
Meitinger, Thomas A.
Germany, Munich
Tum Fakultät Für Medizin
Lenz, Dominic
Germany, Heidelberg
Universitätsklinikum Heidelberg
Ziegler, Andreas E.
Germany, Heidelberg
Universitätsklinikum Heidelberg
Kotzaeridou, Urania
Germany, Heidelberg
Universitätsklinikum Heidelberg
Brunet, Theresa
Germany, Munich
Tum Fakultät Für Medizin
Chassevent, Anna K.
United States, Baltimore
Kennedy Krieger Institute
Smith-Hicks, Constance L.
United States, Baltimore
Kennedy Krieger Institute
United States, Baltimore
Johns Hopkins School of Medicine
Ekstein, Josef
United States, New York
Dor Yeshorim
Weiden, Tzvi
Unknown Affiliation
Hahn, Andreas
Germany, Giessen
Justus-liebig-universität Gießen
Zharkinbekova, N. A.
Kazakhstan, Shymkent
South Kazakhstan Medical Academy
Turnpenny, Peter D.
United Kingdom, Exeter
Royal Devon and Exeter Nhs Foundation Trust
Tucci, Arianna
United Kingdom, London
Queen Mary University of London
Horvàth, Rita
United Kingdom, Cambridge
School of Clinical Medicine
Hız, Semra A.
Turkey, Izmir
Dokuz Eylül Üniversitesi
Lochmüller, Hanns
Canada, Ottawa
Université D'ottawa, Faculté de Médecine
Zollino, Marcella
Italy, Chieti
University of G. D'annunzio Chieti and Pescara
Italy, Rome
Fondazione Policlinico Universitario Agostino Gemelli Irccs
Morleo, Manuela
Italy, Naples
Tigem Telethon Institute of Genetics and Medicine
Nigro, Vincenzo
Italy, Naples
Tigem Telethon Institute of Genetics and Medicine
Italy, Naples
Università Degli Studi Della Campania Luigi Vanvitelli
Torella, Annalaura
Italy, Naples
Tigem Telethon Institute of Genetics and Medicine
Italy, Naples
Università Degli Studi Della Campania Luigi Vanvitelli
Husain, Ralf A.
Germany, Jena
Universitätsklinikum Jena Und Medizinische Fakultät
Grimmel, Mona
Germany, Tubingen
Eberhard Karls Universität Tübingen
Grasshoff, Ute
Germany, Tubingen
Eberhard Karls Universität Tübingen
Korenke, Georg Christoph
Germany, Oldenburg
Universität Oldenburg
Radio, Francesca Clementina
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Mancini, Cecilia
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
McWalter, Kirsty
United States, Gaithersburg
Genedx, Inc.
Begtrup, Amber G.
United States, Gaithersburg
Genedx, Inc.
Crunk, Amy
United States, Gaithersburg
Genedx, Inc.
Guillen-Sacoto, Maria J.
United States, Gaithersburg
Genedx, Inc.
Person, Richard Erwin
United States, Gaithersburg
Genedx, Inc.
Schnur, Rhonda E.
United States, Gaithersburg
Genedx, Inc.
Mancardi, Maria Margherita
Italy, Genoa
Istituto Giannina Gaslini
Striano, Pasquale
Italy, Genoa
Istituto Giannina Gaslini
Italy, Genoa
Università Degli Studi Di Genova
Zara, Federico
Italy, Genoa
Università Degli Studi Di Genova
Italy, Genoa
Istituto Giannina Gaslini
Chung, Wendy Kay
United States, New York
Columbia University
Corbett, Mark A.
Australia, Adelaide
The University of Adelaide
Gécz, J.
Australia, Adelaide
The University of Adelaide
Australia, Adelaide
South Australian Health and Medical Research Institute
Tartaglia, Marco
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Salpietro, Vincenzo Damiano
Italy, Genoa
Istituto Giannina Gaslini
Italy, Genoa
Università Degli Studi Di Genova
Christodoulou, John
Australia, Melbourne
Murdoch Children's Research Institute
Australia, Sydney
The University of Sydney
Padilla-López, Sérgio R.
United States, Phoenix
Barrow Neurological Institute
United States, Phoenix
University of Arizona College of Medicine – Phoenix
Bilgüvar, Kaya
United States, New Haven
Yale University
United States, New Haven
Yale School of Medicine
Münchau, Alexander Maximilian
Germany, Lubeck
Universität zu Lübeck
Ahmed, Zubair M.
United States, Baltimore
University of Maryland, Baltimore Umb
Hufnagel, Robert B.
United States, Bethesda
National Institutes of Health Nih
Fahey, Michael C.
Australia, Clayton
Monash University
Maroofian, Reza
United Kingdom, London
University College London
Houlden, Henry H.
United Kingdom, London
University College London
Sticht, Heinrich
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Mane, Shrikant M.
United States, New Haven
Yale University
United States, New Haven
Yale School of Medicine
Rad, Aboulfazl
Germany, Tubingen
Eberhard Karls Universität Tübingen
Vona, Barbara
Germany, Tubingen
Eberhard Karls Universität Tübingen
Jin, Sheng Chih
United States, St. Louis
Washington University School of Medicine in St. Louis
Haack, Tobias Bernd
Germany, Tubingen
Eberhard Karls Universität Tübingen
Makowski, Christine C.
Germany, Munich
Technische Universität München
Hirsch, Yoel
United States, New York
Dor Yeshorim
Riazuddin, Saima
United States, Baltimore
University of Maryland, Baltimore Umb
Kruer, Michael C.
United States, Phoenix
Barrow Neurological Institute
United States, Phoenix
University of Arizona College of Medicine – Phoenix
Statistics
Citations: 10
Authors: 72
Affiliations: 53
Identifiers
Doi:
10.1016/j.ajhg.2021.08.003
ISSN:
00029297
Research Areas
Disability
Genetics And Genomics
Study Approach
Quantitative