@article{60a6f0cd4d984d5f8d36b010cf4b8fbc,
title = "Loss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder",
abstract = "Purpose: The function of FAM177A1 and its relationship to human disease is largely unknown. Recent studies have demonstrated FAM177A1 to be a critical immune-associated gene. One previous case study has linked FAM177A1 to a neurodevelopmental disorder in 4 siblings. Methods: We identified 5 individuals from 3 unrelated families with biallelic variants in FAM177A1. The physiological function of FAM177A1 was studied in a zebrafish model organism and human cell lines with loss-of-function variants similar to the affected cohort. Results: These individuals share a characteristic phenotype defined by macrocephaly, global developmental delay, intellectual disability, seizures, behavioral abnormalities, hypotonia, and gait disturbance. We show that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA sequencing and metabolomic data sets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation. Conclusion: Our data shed light on the emerging function of FAM177A1 and defines FAM177A1-related neurodevelopmental disorder as a new clinical entity.",
keywords = "Developmental Delay, FAM177A1, Macrocephaly, Neurodevelopment, Zebrafish",
author = "{Undiagnosed Diseases Network} and Kohler, {Jennefer N.} and Legro, {Nicole R.} and Dustin Baldridge and Jimann Shin and Angela Bowman and Berrak Ugur and Jackstadt, {Madelyn M.} and Shriver, {Leah P.} and Patti, {Gary J.} and Bo Zhang and Wenjia Feng and McAdow, {Anthony R.} and Pag{\'e} Goddard and Ungar, {Rachel A.} and Tanner Jensen and Smith, {Kevin S.} and Laure Fresard and Raquel Alvarez and Devon Bonner and Reuter, {Chloe M.} and Colleen McCormack and Elijah Kravets and Shruti Marwaha and Holt, {James M.} and Acosta, {Maria T.} and Margaret Adam and Adams, {David R.} and Alvarez, {Raquel L.} and Justin Alvey and Laura Amendola and Ashley Andrews and Ashley, {Euan A.} and Bacino, {Carlos A.} and Guney Bademci and Ashok Balasubramanyam and Jim Bale and Michael Bamshad and Deborah Barbouth and Pinar Bayrak-Toydemir and Anita Beck and Beggs, {Alan H.} and Edward Behrens and Gill Bejerano and Bellen, {Hugo J.} and Jimmy Bennett and Beverly Berg-Rood and Bernstein, {Jonathan A.} and Berry, {Gerard T.} and Anna Bican and Stephanie Bivona and Elizabeth Blue and John Bohnsack and Lorenzo Botto and Brenna Boyd and Briere, {Lauren C.} and Burke, {Elizabeth A.} and Burrage, {Lindsay C.} and Butte, {Manish J.} and Peter Byers and Byrd, {William E.} and John Carey and Olveen Carrasquillo and Thomas Cassini and Chang, {Ta Chen Peter} and Sirisak Chanprasert and Chao, {Hsiao Tuan} and Ivan Chinn and Clark, {Gary D.} and Coakley, {Terra R.} and Cobban, {Laurel A.} and Cogan, {Joy D.} and Matthew Coggins and {Sessions Cole}, F. and Colley, {Heather A.} and Heidi Cope and Brian Corner and Rosario Corona and Craigen, {William J.} and Crouse, {Andrew B.} and Michael Cunningham and Precilla D'Souza and Hongzheng Dai and Surendra Dasari and Joie Davis and Dayal, {Jyoti G.} and Dell'Angelica, {Esteban C.} and Patricia Dickson and Katrina Dipple and Daniel Doherty and Naghmeh Dorrani and Doss, {Argenia L.} and Douine, {Emilie D.} and Dawn Earl and Eckstein, {David J.} and Emrick, {Lisa T.} and Eng, {Christine M.} and Kimberly Ezell and Marni Falk and Fieg, {Elizabeth L.} and Fisher, {Paul G.} and Fogel, {Brent L.} and Irman Forghani and Gahl, {William A.} and Ian Glass and Bernadette Gochuico and Goddard, {Page C.} and Godfrey, {Rena A.} and Katie Golden-Grant and Alana Grajewski and Don Hadley and Sihoun Hahn and Halley, {Meghan C.} and Rizwan Hamid and Kelly Hassey and Nichole Hayes and Frances High and Anne Hing and Hisama, {Fuki M.} and Holm, {Ingrid A.} and Jason Hom and Martha Horike-Pyne and Alden Huang and Sarah Hutchison and Wendy Introne and Rosario Isasi and Kosuke Izumi and Fariha Jamal and Jarvik, {Gail P.} and Jeffrey Jarvik and Suman Jayadev and Orpa Jean-Marie and Vaidehi Jobanputra and Lefkothea Karaviti and Shamika Ketkar and Dana Kiley and Gonench Kilich and Kobren, {Shilpa N.} and Kohane, {Isaac S.} and Susan Korrick and Mary Kozuira and Deborah Krakow and Krasnewich, {Donna M.} and Lalani, {Seema R.} and Byron Lam and Christina Lam and Lanpher, {Brendan C.} and Lanza, {Ian R.} and Kimberly LeBlanc and Lee, {Brendan H.} and Roy Levitt and Lewis, {Richard A.} and Pengfei Liu and Liu, {Xue Zhong} and Nicola Longo and Loo, {Sandra K.} and Joseph Loscalzo and Maas, {Richard L.} and Macnamara, {Ellen F.} and MacRae, {Calum A.} and Maduro, {Valerie V.} and Maghiro, {Audrey Stephannie} and Rachel Mahoney and Malicdan, {May Christine V.} and Mamounas, {Laura A.} and Manolio, {Teri A.} and Rong Mao and Kenneth Maravilla and Ronit Marom and Gabor Marth and Martin, {Beth A.} and Martin, {Martin G.} and Mart{\'i}nez-Agosto, {Julian A.} and Jacob McCauley and Allyn McConkie-Rosell and McCray, {Alexa T.} and Elisabeth McGee and Heather Mefford and {Lawrence Merritt}, J. and Matthew Might and Ghayda Mirzaa and Eva Morava and Paolo Moretti and John Mulvihill and Mariko Nakano-Okuno and Nelson, {Stanley F.} and Serena Neumann and Newman, {John H.} and Nicholas, {Sarah K.} and Deborah Nickerson and Shirley Nieves-Rodriguez and Donna Novacic and Devin Oglesbee and Orengo, {James P.} and Laura Pace and Stephen Pak and {Carl Pallais}, J. and Palmer, {Christina G.S.} and Timothy Schedl and Lilianna Solnica-Krezel and Jennifer Wambach",
note = "Publisher Copyright: {\textcopyright} 2024 American College of Medical Genetics and Genomics",
year = "2024",
month = sep,
doi = "10.1016/j.gim.2024.101166",
language = "English",
volume = "26",
journal = "Genetics in Medicine",
issn = "1098-3600",
number = "9",
}