例如:"lncRNA", "apoptosis", "WRKY"

Phenotypic spectrum associated with a CRADD founder variant underlying frontotemporal predominant pachygyria in the Finnish population.

Eur J Hum Genet. 2019 Aug;27(8):1235-1243. Epub 2019 Mar 26
Daniel L Polla 1 , Elisa Rahikkala 2 , Michaela K Bode 3 , Tuomo Määttä 4 , Teppo Varilo 5 , Thyrza Loman 6 , Anju K Philips 5 , Mitja Kurki 7 , Aarno Palotie 8 , Jarmo Körkkö 9 , Päivi Vieira 10 , Kristiina Avela 11 , Valérie Jacquemin 12 , Isabelle Pirson 12 , Marc Abramowicz 12 , Arjan P M de Brouwer 6 , Outi Kuismin 7 , Hans van Bokhoven 6 , Irma Järvelä 13
Daniel L Polla 1 , Elisa Rahikkala 2 , Michaela K Bode 3 , Tuomo Määttä 4 , Teppo Varilo 5 , Thyrza Loman 6 , Anju K Philips 5 , Mitja Kurki 7 , Aarno Palotie 8 , Jarmo Körkkö 9 , Päivi Vieira 10 , Kristiina Avela 11 , Valérie Jacquemin 12 , Isabelle Pirson 12 , Marc Abramowicz 12 , Arjan P M de Brouwer 6 , Outi Kuismin 7 , Hans van Bokhoven 6 , Irma Järvelä 13
+ et al

[No authors listed]

Author information
  • 1 CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
  • 2 Department of Clinical Genetics, PEDEGO Research Unit and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
  • 3 Department of Diagnostic Radiology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
  • 4 Disability Services, Joint Authority for Kainuu, Kainuu, Finland.
  • 5 Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
  • 6 Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 7 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • 8 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • 9 Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care, 90220, Oulu, Finland.
  • 10 Clinic for Children and Adolescents, PEDEGO Research Unit and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
  • 11 Department of Clinical Genetics, Helsinki University Hospital, Helsinki, Finland.
  • 12 Medical Genetics, IRIBHM, Université Libre de Bruxelles, Brussels, Belgium.
  • 13 Department of Medical Genetics, University of Helsinki, Helsinki, Finland. irma.jarvela@helsinki.fi.

摘要


Intellectual disability (ID), megalencephaly, frontal predominant pachygyria, and seizures, previously called "thin" lissencephaly, are reported to be caused by recessive variants in CRADD. Among five families of different ethnicities identified, one homozygous missense variant, c.509G>A p.(Arg170His), was of Finnish ancestry. Here we report on the phenotypic variability associated for this potential CRADD founder variant in 22 Finnish individuals. Exome sequencing was used to identify candidate genes in Finnish patients presenting with ID. Targeted Sanger sequencing and restriction enzyme analysis were applied to screen for the c.509G>A CRADD variant in cohorts from Finland. Detailed phenotyping and genealogical studies were performed. Twenty two patients were identified with the c.509G>A p.(Arg170His) homozygous variant in CRADD. The majority of the ancestors originated from Northeastern Finland indicating a founder effect. The hallmark of the disease is frontotemporal predominant pachygyria with mild cortical thickening. All patients show ID of variable severity. Aggressive behavior was found in nearly half of the patients, EEG abnormalities in five patients and megalencephaly in three patients. This study provides detailed data about the phenotypic spectrum of patients with lissencephaly due to a CRADD variant that affects function. High inter- and intrafamilial phenotypic heterogeneity was identified in patients with pachygyria caused by the homozygous CRADD founder variant. The phenotype variability suggests that additional genetic and/or environmental factors play a role in the clinical presentation. Since frontotemporal pachygyria is the hallmark of the disease, brain imaging studies are essential to support the molecular diagnosis for individuals with ID and a CRADD variant.