Ferdy K Cayami1, Roberta La Piana2, Rosalina M L van Spaendonk3, Miriam Nickel4, Annette Bley4, Kether Guerrero2, Luan T Tran2, Marjo S van der Knaap1, Geneviève Bernard2, Nicole I Wolf1. 1. Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands. 2. Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, McGill University Health Center, Montreal, Canada. 3. Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. 4. Department of Pediatrics, Clinic for Degenerative Brain Disorders, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Abstract
OBJECTIVE: This study aims to ascertain frequency of mutations in POLR3A or POLR3B, which are associated with 4H leukodystrophy, in a cohort of patients with unclassified hypomyelination. METHODS AND RESULTS: In a cohort of 22 patients with the magnetic resonance imaging (MRI) diagnosis of unclassified hypomyelination and without typical clinical signs, we evaluated clinical and MRI features. Developmental delay or intellectual disability, ataxia, and spasticity were frequent symptoms. POLR3A and POLR3B were sequenced. A compound heterozygote mutation in POLR3B was found in only one patient. Additional investigations allowed a definitive diagnosis in 10 patients. CONCLUSION: Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination, and alternative diagnoses should be considered first. Georg Thieme Verlag KG Stuttgart · New York.
OBJECTIVE: This study aims to ascertain frequency of mutations in POLR3A or POLR3B, which are associated with 4H leukodystrophy, in a cohort of patients with unclassified hypomyelination. METHODS AND RESULTS: In a cohort of 22 patients with the magnetic resonance imaging (MRI) diagnosis of unclassified hypomyelination and without typical clinical signs, we evaluated clinical and MRI features. Developmental delay or intellectual disability, ataxia, and spasticity were frequent symptoms. POLR3A and POLR3B were sequenced. A compound heterozygote mutation in POLR3B was found in only one patient. Additional investigations allowed a definitive diagnosis in 10 patients. CONCLUSION: Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination, and alternative diagnoses should be considered first. Georg Thieme Verlag KG Stuttgart · New York.
Authors: Laurence Gauquelin; Martine Tétreault; Isabelle Thiffault; Emily Farrow; Neil Miller; Byunggil Yoo; Eric Bareke; Grace Yoon; Oksana Suchowersky; Nicolas Dupré; Mark Tarnopolsky; Bernard Brais; Nicole I Wolf; Jacek Majewski; Guy A Rouleau; Ziv Gan-Or; Geneviève Bernard Journal: Brain Date: 2018-01-01 Impact factor: 13.501
Authors: Martina Minnerop; Delia Kurzwelly; Holger Wagner; Anne S Soehn; Jennifer Reichbauer; Feifei Tao; Tim W Rattay; Michael Peitz; Kristina Rehbach; Alejandro Giorgetti; Angela Pyle; Holger Thiele; Janine Altmüller; Dagmar Timmann; Ilker Karaca; Martina Lennarz; Jonathan Baets; Holger Hengel; Matthis Synofzik; Burcu Atasu; Shawna Feely; Marina Kennerson; Claudia Stendel; Tobias Lindig; Michael A Gonzalez; Rüdiger Stirnberg; Marc Sturm; Sandra Roeske; Johanna Jung; Peter Bauer; Ebba Lohmann; Stefan Herms; Stefanie Heilmann-Heimbach; Garth Nicholson; Muhammad Mahanjah; Rajech Sharkia; Paolo Carloni; Oliver Brüstle; Thomas Klopstock; Katherine D Mathews; Michael E Shy; Peter de Jonghe; Patrick F Chinnery; Rita Horvath; Jürgen Kohlhase; Ina Schmitt; Michael Wolf; Susanne Greschus; Katrin Amunts; Wolfgang Maier; Ludger Schöls; Peter Nürnberg; Stephan Zuchner; Thomas Klockgether; Alfredo Ramirez; Rebecca Schüle Journal: Brain Date: 2017-06-01 Impact factor: 13.501
Authors: Roberta La Piana; Ferdy K Cayami; Luan T Tran; Kether Guerrero; Rosalina van Spaendonk; Katrin Õunap; Sander Pajusalu; Tobias Haack; Evangeline Wassmer; Dagmar Timmann; Hanna Mierzewska; Bwee T Poll-Thé; Chirag Patel; Helen Cox; Tahir Atik; Huseyin Onay; Ferda Ozkınay; Adeline Vanderver; Marjo S van der Knaap; Nicole I Wolf; Geneviève Bernard Journal: Neurology Date: 2016-03-30 Impact factor: 9.910
Authors: Karine Choquet; Sharon Yang; Robyn D Moir; Diane Forget; Roxanne Larivière; Annie Bouchard; Christian Poitras; Nicolas Sgarioto; Marie-Josée Dicaire; Forough Noohi; Timothy E Kennedy; Joseph Rochford; Geneviève Bernard; Martin Teichmann; Benoit Coulombe; Ian M Willis; Claudia L Kleinman; Bernard Brais Journal: Mol Brain Date: 2017-04-13 Impact factor: 4.041
Authors: Vassos Neocleous; Pavlos Fanis; Meropi Toumba; George A Tanteles; Melpo Schiza; Feride Cinarli; Nicolas C Nicolaides; Anastasis Oulas; George M Spyrou; Christos S Mantzoros; Dimitrios Vlachakis; Nicos Skordis; Leonidas A Phylactou Journal: Front Endocrinol (Lausanne) Date: 2020-08-28 Impact factor: 5.555