Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature. Issue 6 (3rd August 2020)

• Record Type: Journal Article
• Authors: Johnstone, Devon L.; Nguyen, Thi Tuyet Mai; Zambonin, Jessica; Kernohan, Kristin D.; St‐Denis, Anik; Baratang, Nissan V.; Hartley, Taila; Geraghty, Michael T.; Richer, Julie; Majewski, Jacek; Bareke, Eric; Guerin, Andrea; Pendziwiat, Manuela; Pena, Loren D. M.; Braakman, Hilde M. H.; Gripp, Karen W.; Edmondson, Andrew C.; He, Miao; Spillmann, Rebecca C.; Eklund, Erik A.; Bayat, Allan; McMillan, Hugh J.; Boycott, Kym M.; Campeau, Philippe M.
• Other Names: Acosta Maria T. investigator.; Adam Margaret investigator.; Adams David R. investigator.; Agrawal Pankaj B. investigator.; Alejandro Mercedes E. investigator.; Alvey Justin investigator.; Amendola Laura investigator.; Andrews Ashley investigator.; Ashley Euan A. investigator.; Azamian Mahshid S. investigator.; Bacino Carlos A. investigator.; Bademci Guney investigator.; Baker Eva investigator.; Balasubramanyam Ashok investigator.; Baldridge Dustin investigator.; Bale Jim investigator.; Bamshad Michael investigator.; Barham Jordan investigator.; Barbouth Deborah investigator.; Batzli Gabriel F. investigator.; Bayrak‐Toydemir Pinar investigator.; Beck Anita investigator.; Beggs Alan H. investigator.; Bejerano Gill investigator.; Bennet Jimmy investigator.; Berg‐Rood Beverly investigator.; Bernier Raphael investigator.; Bernstein Jonathan A. investigator.; Berry Gerard T. investigator.; Bican Anna investigator.; Bivona Stephanie investigator.; Blue Elizabeth investigator.; Bohnsack John investigator.; Bonnenmann Carsten investigator.; Bonner Devon investigator.; Botto Lorenzo investigator.; Boyd Brenna investigator.; Briere Lauren C. investigator.; Brokamp Elly investigator.; Brown Gabrielle investigator.; Burke Elizabeth A. investigator.; Burrage Lindsay C. investigator.; Butte Manish J. investigator.; Byers Peter investigator.; Byrd William E. investigator.; Carey John investigator.; Carrasquillo Olveen investigator.; Chang Ta Chen Peter investigator.; Chanprasert Sirisak investigator.; Chao Hsiao‐Tuan investigator.; Chen Mei‐Jan investigator.; Clark Gary D. investigator.; Coakley Terra R. investigator.; Cobban Laurel A. investigator.; Cogan Joy D. investigator.; Cole F. Sessions investigator.; Colley Heather A. investigator.; Cooper Cynthia M. investigator.; Cope Heidi investigator.; Craigen William J. investigator.; Cunningham Michael investigator.; D'Souza Precilla investigator.; Dai Hongzheng investigator.; Dasari Surendra investigator.; Davids Mariska investigator.; Dayal Jyoti G. investigator.; Dell'Angelica Esteban C. investigator.; Dhar Shweta U. investigator.; Dipple Katrina investigator.; Doherty Daniel investigator.; Dorrani Naghmeh investigator.; Douine Emilie D. investigator.; Draper David D. investigator.; Duncan Laura investigator.; Earl Dawn investigator.; Eckstein David J. investigator.; Emrick Lisa T. investigator.; Eng Christine M. investigator.; Esteves Cecilia investigator.; Estwick Tyra investigator.; Fernandez Liliana investigator.; Ferreira Carlos investigator.; Fieg Elizabeth L. investigator.; Fisher Paul G. investigator.; Fogel Brent L. investigator.; Forghani Irman investigator.; Fresard Laure investigator.; Gahl William A. investigator.; Glass Ian investigator.; Godfrey Rena A. investigator.; Golden‐Grant Katie investigator.; Goldman Alica M. investigator.; Goldstein David B. investigator.; Grajewski Alana investigator.; Groden Catherine A. investigator.; Gropman Andrea L. investigator.; Hahn Sihoun investigator.; Hamid Rizwan investigator.; Hanchard Neil A. investigator.; Hayes Nichole investigator.; High Frances investigator.; Hing Anne investigator.; Hisama Fuki M. investigator.; Holm Ingrid A. investigator.; Hom Jason investigator.; Horike‐Pyne Martha investigator.; Huang Alden investigator.; Huang Yong investigator.; Isasi Rosario investigator.; Jamal Fariha investigator.; Jarvik Gail P. investigator.; Jarvik Jeffrey investigator.; Jayadev Suman investigator.; Johnston Jean M. investigator.; Karaviti Lefkothea investigator.; Kelley Emily G. investigator.; Kiley Dana investigator.; Kohane Isaac S. investigator.; Kohler Jennefer N. investigator.; Krakow Deborah investigator.; Krasnewich Donna M. investigator.; Korrick Susan investigator.; Koziura Mary investigator.; Krier Joel B. investigator.; Lalani Seema R. investigator.; Lam Byron investigator.; Lam Christina investigator.; Lanpher Brendan C. investigator.; Lanza Ian R. investigator.; Lau C. Christopher investigator.; LeBlanc Kimberly investigator.; Lee Brendan H. investigator.; Lee Hane investigator.; Levitt Roy investigator.; Lewis Richard A. investigator.; Lincoln Sharyn A. investigator.; Liu Pengfei investigator.; Liu Xue Zhong investigator.; Longo Nicola investigator.; Loo Sandra K. investigator.; Loscalzo Joseph investigator.; Maas Richard L. investigator.; Macnamara Ellen F. investigator.; MacRae Calum A. investigator.; Maduro Valerie V. investigator.; Majcherska Marta M. investigator.; Malicdan May Christine V. investigator.; Mamounas Laura A. investigator.; Manolio Teri A. investigator.; Mao Rong investigator.; Maravilla Kenneth investigator.; Markello Thomas C. investigator.; Marom Ronit investigator.; Marth Gabor investigator.; Martin Beth A. investigator.; Martin Martin G. investigator.; Martínez‐Agosto Julian A. investigator.; Marwaha Shruti investigator.; McCauley Jacob investigator.; McConkie‐Rosell Allyn investigator.; McCormack Colleen E. investigator.; McCray Alexa T. investigator.; McGee Elisabeth investigator.; Mefford Heather investigator.; Merritt J. Lawrence investigator.; Might Matthew investigator.; Mirzaa Ghayda investigator.; Morava‐Kozicz Eva investigator.; Moretti Paolo M. investigator.; Morimoto Marie investigator.; Mulvihill John J. investigator.; Murdock David R. investigator.; Nakano‐Okuno Mariko investigator.; Nath Avi investigator.; Nelson Stan F. investigator.; Newman John H. investigator.; Nicholas Sarah K. investigator.; Nickerson Deborah investigator.; Novacic Donna investigator.; Oglesbee Devin investigator.; Orengo James P. investigator.; Pace Laura investigator.; Pak Stephen investigator.; Pallais J. Carl investigator.; Palmer Christina GS. investigator.; Papp Jeanette C. investigator.; Parker Neil H. investigator.; Phillips John A. investigator.; Posey Jennifer E. investigator.; Potocki Lorraine investigator.; Pusey Barbara N. investigator.; Quinlan Aaron investigator.; Raskind Wendy investigator.; Raja Archana N. investigator.; Renteria Genecee investigator.; Reuter Chloe M. investigator.; Rives Lynette investigator.; Robertson Amy K. investigator.; Rodan Lance H. investigator.; Rosenfeld Jill A. investigator.; Rosenwasser Natalie investigator.; Rowley Robb K. investigator.; Ruzhnikov Maura investigator.; Sacco Ralph investigator.; Sampson Jacinda B. investigator.; Samson Susan L. investigator.; Saporta Mario investigator.; Scott C. Ron investigator.; Schaechter Judy investigator.; Schedl Timothy investigator.; Schoch Kelly investigator.; Scott Daryl A. investigator.; Shakachite Lisa investigator.; Sharma Prashant investigator.; Shashi Vandana investigator.; Shin Jimann investigator.; Signer Rebecca investigator.; Sillari Catherine H. investigator.; Silverman Edwin K. investigator.; Sinsheimer Janet S. investigator.; Sisco Kathy investigator.; Smith Edward C. investigator.; Smith Kevin S. investigator.; Solnica‐Krezel Lilianna investigator.; Spillmann Rebecca C. investigator.; Stoler Joan M. investigator.; Stong Nicholas investigator.; Sullivan Jennifer A. investigator.; Sun Angela investigator.; Sutton Shirley investigator.; Sweetser David A. investigator.; Sybert Virginia investigator.; Tabor Holly K. investigator.; Tamburro Cecelia P. investigator.; Tan Queenie K.‐G. investigator.; Tekin Mustafa investigator.; Telischi Fred investigator.; Thorson Willa investigator.; Tifft Cynthia J. investigator.; Toro Camilo investigator.; Tran Alyssa A. investigator.; Urv Tiina K. investigator.; Velinder Matt investigator.; Viskochil Dave investigator.; Vogel Tiphanie P. investigator.; Wahl Colleen E. investigator.; Wallace Stephanie investigator.; Walley Nicole M. investigator.; Walsh Chris A. investigator.; Walker Melissa investigator.; Wambach Jennifer investigator.; Wan Jijun investigator.; Wang Lee‐kai investigator.; Wangler Michael F. investigator.; Ward Patricia A. investigator.; Wegner Daniel investigator.; Wener Mark investigator.; Wenger Tara investigator.; Perry Katherine Wesseling investigator.; Westerfield Monte investigator.; Wheeler Matthew T. investigator.; Wise Anastasia L. investigator.; Wolfe Lynne A. investigator.; Woods Jeremy D. investigator.; Yamamoto Shinya investigator.; Yang John investigator.; Yu Guoyun investigator.; Zastrow Diane B. investigator.; Zhao Chunli investigator.; Zuchner Stephan investigator.;
• Is Part Of: Journal of inherited metabolic disease. Volume 43:Issue 6(2020)
• Page Start: 1321
• Page End: 1332
• Publication Date: 2020-08-03
• Subjects: epileptic encephalopathy -- exome sequencing -- GPI -- IGD -- PIGQ -- rare diseases; Metabolism, Inborn errors of -- Periodicals; Metabolism -- Disorders -- Periodicals; 616.39042
• DOI: 10.1002/jimd.12278
• Languages: English
• ISSNs: 0141-8955

Abstract

Abstract: We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q ( PIGQ ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)‐anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ ‐related disease and provide the first functional evidence in human cells of defective GPI‐anchoring due to pathogenic variants in PIGQ.