title: Recessive Mutations in POLR3B Encoding RNA Polymerase III Subunit Causing Diffuse Hypomyelination in Patients with 4H Leukodystrophy with Polymicrogyria and Cataracts.
abstract: The diagnosis of 4H leukodystrophy (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) is based on clinical findings and magnetic resonance imaging (MRI). Recently, mutations of the genes encoding Pol III (RNA polymerase III) subunit A (POLR3A) and subunit B (POL3B) have been identified as the genetic causes of hypomyelination. We describe two Polish female siblings aged 5 and 10 years with compound heterozygous mutations in POLR3B. They both presented with similar clinical symptoms and MRI findings presenting as 4H leukodystrophy, and the association of polymicrogyria and cataract. According to our observation in young children with the absence of hypogonadotropic hypogonadism, brain MRI pattern is very essential in proper early diagnosis of 4H leukodystrophy. All clinical and radiological results are of course helpful, however genetic conformation is always necessary.
authors.affiliation: Department of Diagnostic Imaging, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland. e-jurkiewicz@o2.pl.
authors.forename: E
authors.initials: E
authors.lastname: Jurkiewicz
authors.affiliation: Neurology and Epileptology Department, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Dunin-Wąsowicz
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland.|Department of Paediatrics, The Medical University of Warsaw, Dzialdowska1, 01-184, Warsaw, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Gieruszczak-Białek
authors.affiliation: Department of Diagnostic Imaging, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Malczyk
authors.affiliation: Pediatric Neurodegenerative Laboratory, Departments of Neurology and Neurosurgery and Pediatrics, McGill University Health Center Research Institute, McGill Universit, Montreal, Quebec, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Guerrero
authors.affiliation: Pediatric Neurodegenerative Laboratory, Departments of Neurology and Neurosurgery and Pediatrics, McGill University Health Center Research Institute, McGill Universit, Montreal, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Gutierrez
authors.affiliation: Pediatric Neurodegenerative Laboratory, Departments of Neurology and Neurosurgery and Pediatrics, McGill University Health Center Research Institute, McGill Universit, Montreal, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Tran
authors.affiliation: Pediatric Neurodegenerative Laboratory, Departments of Neurology and Neurosurgery and Pediatrics, McGill University Health Center Research Institute, McGill Universit, Montreal, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Bernard
mesh_terms: D002386:Cataract / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D065706:Polymicrogyria / Q000000981:diagnostic imaging / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012320:RNA Polymerase III / Q000235:genetics*
chemical_list: C468558:POLR3B protein, human; D012320:RNA Polymerase III
keywords: 4H leukodystrophy; Cataract; Children; Hypomyelination; Magnetic resonance imaging; Polymicrogyria