{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Morimoto M"],"funding":["NHGRI NIH HHS","Canadian Institutes of Health (CIHR)","National Institutes of Health (NIH) Common Fund","U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute"],"pagination":["4"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9918471"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(1)"],"pubmed_abstract":["Autophagy regulates the degradation of damaged organelles and protein aggregates, and is critical for neuronal development, homeostasis, and maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis, a hallmark of autophagy. Autophagosome biogenesis and induction of autophagy were intact in cells from affected individuals. However, studies evaluating the predominant substrate of ATG4D, GABARAP"],"journal":["NPJ genomic medicine"],"pubmed_title":["Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment."],"pmcid":["PMC9918471"],"funding_grant_id":["U01 HG007703"],"pubmed_authors":["Dasari S","Cole FS","Undiagnosed Diseases Network","Liu XZ","Emrick LT","Solem E","Wener M","Gutierrez I","Novacic D","Malicdan MCV","Worley K","Sutton S","Cunningham M","Amendola L","Butte MJ","Jobanputra V","Walker M","Stoler JM","Jean-Marie O","Bonner D","Kozuira M","Cooper CM","Weisz Hubshman M","Wesseling Perry K","Loo SK","Smith EC","Hahn S","Coakley TR","Sathiyaseelan P","Pallais JC","Fieg EL","Papp JC","Bellen HJ","Acosta MT","Chang TCP","Posey JE","Lanza IR","Silverman EK","Forghani I","Dayal JG","Jarvik GP","Vogel TP","Adams DR","Duncan L","Krakow D","Byers P","Martin MG","Azamian MS","Bale J","Fisher PG","Fogel BL","Mahoney R","Renteria G","Sinsheimer JS","Lanpher BC","Izumi K","Scott DA","McCray AT","Phillips JA","Whitlock J","Newman JH","Scott CR","Murphy JL","Sweetser DA","Adam M","Alvey J","Tran AA","Macnamara EF","Gochuico B","Carrasquillo O","Cobban LA","Nickerson D","Berg-Rood B","Raper A","Davis J","Marth G","Cogan JD","Schaechter J","Wang LK","Lange J","Nicholas SK","Bivona S","Tabor HK","Wenger T","Pusey Swerdzewski BN","Bejerano G","Jarvik J","Craigen WJ","Might M","Boyd B","Kennedy J","Isasi R","Wangler MF","Karaviti L","Pak S","Zuchner S","Bayrak-Toydemir P","Hisama FM","Martin BA","Hayes N","Longo N","Ketkar S","Rosenfeld JA","Gorski SM","Jamal F","Mao R","Liu P","Sullivan K","Mamounas LA","Wallace S","Wambach J","Alvarez RL","Lalani SR","Thurm A","Dorrani N","Parker NH","Blue E","Palmer CGS","Saporta M","Orengo JP","Thorson W","Telischi F","Wheeler MT","Hing A","Horike-Pyne M","Martinez-Agosto JA","Bennett J","Kilich G","Bamshad M","Zhang Z","Tekin M","Eng CM","D'Souza P","Hom J","Kravets E","Boerkoel CF","Nelson SF","Halley MC","Smith KS","Sybert V","Krasnewich DM","Bohnsack J","Urv TK","Tifft CJ","Wan J","Baldridge D","Lewis RA","Holm IA","Sacco R","Solomon B","Solnica-Krezel L","Clark GD","Gazzaz N","Mak BC","McCauley J","Rodan LH","Byrd WE","Kohane IS","Nieves-Rodriguez S","Beck A","Moretti P","Potocki L","Grajewski A","Crouse AB","Glass I","Lehman A","Wegner D","Doss AL","Hutchison S","Rives L","Coggins M","Andrews A","Kiley D","Kohler JN","Zerfas PM","Shashi V","Behrens E","Tan ALM","Botto L","Davids M","Ashley EA","Bacino CA","Chanprasert S","Eckstein DJ","Barbouth D","Briere LC","Quinlan A","Ruzhnikov M","Maravilla K","Beggs AH","Marwaha S","Nakano-Okuno M","Hamid R","Reichert S","Reuter CM","Xiao C","Dai H","Spillmann RC","Goddard PC","Sisco K","Bhambhani V","Sun A","Wang C","Vanderver A","Morimoto M","Balasubramanyam A","Burrage LC","Shin J","Brown G","Schoch K","Marom R","Ungar RA","Manolio TA","Toro C","Pace L","Lee BH","Cassini T","Chao HT","Esteves C","Huang A","Oglesbee D","Introne WJ","Velinder M","Yang J","McConkie-Rosell A","Morava E","Maduro VV","Yamamoto S","Viskochil D","Carey J","Sampson JB","Levitt R","Merritt JL","Bademci G","Falk M","High F","Bernstein JA","Berry GT","Bican A","Burke EA","Brokamp E","Kobren SN","Lam B","LeBlanc K","Lam C","Rossignol F","Walley NM","Robertson AK","Hassey K","Cope H","Ward PA","Earl D","McGee E","MacRae CA","Mefford H","Alderman E","Sullivan JA","Doherty D","Mirzaa G","Rosenwasser N","Maas RL","Gahl WA","Colley HA","Loscalzo J","Schedl T","Jayadev S","Rao DA","Hadley D","Dipple K","Wolfe LA","Korrick S","Raskind W","Dell'Angelica EC","Godfrey RA","Tan QK","Westerfield M","Douine ED","Wahl CE","Golden-Grant K"],"additional_accession":[]},"is_claimable":false,"name":"Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment.","description":"Autophagy regulates the degradation of damaged organelles and protein aggregates, and is critical for neuronal development, homeostasis, and maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis, a hallmark of autophagy. Autophagosome biogenesis and induction of autophagy were intact in cells from affected individuals. However, studies evaluating the predominant substrate of ATG4D, GABARAP","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-07-14T21:07:22.554Z","creation":"2025-04-06T00:50:56.813Z"},"accession":"S-EPMC9918471","cross_references":{"pubmed":["36765070"],"doi":["10.1038/s41525-022-00343-8"]}}