例如:"lncRNA", "apoptosis", "WRKY"

Molecular and clinical spectra of FBXL4 deficiency.

Hum. Mutat.2017 Dec;38(12):1649-1659. doi:10.1002/humu.23341. Epub 2017 Oct 06
Ayman W El-Hattab 1 , Hongzheng Dai 2 , Mohammed Almannai 2 , Julia Wang 3 , Eissa A Faqeih 4 , Ali Al Asmari 4 , Mohammed A M Saleh 4 , Mohammed A O Elamin 4 , Majid Alfadhel 5 , Fowzan S Alkuraya 6 , Mais Hashem 7 , Mazhor S Aldosary 7 , Rawan Almass 7 , Faten B Almutairi 7 , Maysoon Alsagob 7 , Mohammed Al-Owain 8 , Shirin Al-Sharfa 8 , Zuhair N Al-Hassnan 8 , Zuhair Rahbeeni 8 , Mohammed A Al-Muhaizea 9 , Nawal Makhseed 10 , Gretchen K Foskett 11 , David A Stevenson 11 , Natalia Gomez-Ospina 11 , Chung Lee 11 , Richard G Boles 12 , Samantha A Schrier Vergano 13 , Saskia B Wortmann 14 , Wolfgang Sperl 15 , Thomas Opladen 16 , Georg F Hoffmann 16 , Maja Hempel 17 , Holger Prokisch 14 , Bader Alhaddad 14 , Johannes A Mayr 18 , Wenyaw Chan 19 , Namik Kaya 7 , Lee-Jun C Wong 2
Ayman W El-Hattab 1 , Hongzheng Dai 2 , Mohammed Almannai 2 , Julia Wang 3 , Eissa A Faqeih 4 , Ali Al Asmari 4 , Mohammed A M Saleh 4 , Mohammed A O Elamin 4 , Majid Alfadhel 5 , Fowzan S Alkuraya 6 , Mais Hashem 7 , Mazhor S Aldosary 7 , Rawan Almass 7 , Faten B Almutairi 7 , Maysoon Alsagob 7 , Mohammed Al-Owain 8 , Shirin Al-Sharfa 8 , Zuhair N Al-Hassnan 8 , Zuhair Rahbeeni 8 , Mohammed A Al-Muhaizea 9 , Nawal Makhseed 10 , Gretchen K Foskett 11 , David A Stevenson 11 , Natalia Gomez-Ospina 11 , Chung Lee 11 , Richard G Boles 12 , Samantha A Schrier Vergano 13 , Saskia B Wortmann 14 , Wolfgang Sperl 15 , Thomas Opladen 16 , Georg F Hoffmann 16 , Maja Hempel 17 , Holger Prokisch 14 , Bader Alhaddad 14 , Johannes A Mayr 18 , Wenyaw Chan 19 , Namik Kaya 7 , Lee-Jun C Wong 2
+ et al

[No authors listed]

Author information
  • 1 Division of Clinical Genetics and Metabolic Disorders, Pediatric Department, Tawam Hospital, Al-Ain, United Arab Emirates.
  • 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
  • 3 Medical Scientist Training Program and Program in Developmental Biology, Baylor College of Medicine, Houston, Texas.
  • 4 Section of Medical Genetics, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
  • 5 Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.
  • 6 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
  • 7 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 8 Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • 9 Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • 10 Department of Pediatrics, Al-Jahra Hospital, Ministry of Health, Al-Jahra City, Kuwait.
  • 11 Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
  • 12 Lineagen, Salt Lake City, Utah.
  • 13 Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia.
  • 14 Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
  • 15 Department of Pediatrics, Salzburger Landeskliniken, Paracelsus Medical University, Salzburg, Austria.
  • 16 Centre for Child and Adolescent Medicine, Divisions of General Pediatrics, Neuropediatrics, and Metabolic Medicine, University Hospital, Heidelberg, Germany.
  • 17 Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • 18 Department of Pediatrics, Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 19 Department of Biostatistics, School of Public Health, University of Texas-Health Science Center at Houston, Houston, Texas.

摘要


F-box and leucine-rich repeat protein 4 (FBXL4) is a mitochondrial protein whose exact function is not yet known. However, cellular studies have suggested that it plays significant roles in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) maintenance, and mitochondrial dynamics. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multisystem disease characterized by lactic acidemia, developmental delay, and hypotonia. Other features are feeding difficulties, growth failure, microcephaly, hyperammonemia, seizures, hypertrophic cardiomyopathy, elevated liver transaminases, recurrent infections, variable distinctive facial features, white matter abnormalities and cerebral atrophy found in neuroimaging, combined deficiencies of multiple electron transport complexes, and mtDNA depletion. Since its initial description in 2013, 36 different pathogenic variants in FBXL4 were reported in 50 affected individuals. In this report, we present 37 additional affected individuals and 11 previously unreported pathogenic variants. We summarize the clinical features of all 87 individuals with FBXL4-related mtDNA maintenance defect, review FBXL4 structure and function, map the 47 pathogenic variants onto the gene structure to assess the variants distribution, and investigate the genotype-phenotype correlation. Finally, we provide future directions to understand the disease mechanism and identify treatment strategies.

KEYWORDS: FBXL4, mitochondrial DNA depletion, mitochondrial DNA maintenance, mitochondrial diseases, mtDNA