2. Academic Validation
  3. CNP deficiency causes severe hypomyelinating leukodystrophy in humans

CNP deficiency causes severe hypomyelinating leukodystrophy in humans

  • Hum Genet. 2020 May;139(5):615-622. doi: 10.1007/s00439-020-02144-4.
Lama Al-Abdi 1 2,  Fathiya Al Murshedi 3,  Alaa Elmanzalawy 4,  Asila Al Habsi 5,  Rana Helaby 1,  Anuradha Ganesh 6,  Niema Ibrahim 1,  Nisha Patel 1,  Fowzan S Alkuraya 7 8
Affiliations

Affiliations

  • 1 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 2 Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
  • 3 Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman.
  • 4 Department of Radiology and Molecular Imaging, Sultan Qaboos University Hospital, Muscat, Oman.
  • 5 Department of Nursing, Sultan Qaboos University, Muscat, Oman.
  • 6 Department of Ophthalmology, Sultan Qaboos University, Muscat, Oman.
  • 7 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
  • 8 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
PMID: 32128616 DOI: 10.1007/s00439-020-02144-4
Abstract

Myelin pathologies are an important cause of multifactorial, e.g., multiple sclerosis, and Mendelian, e.g., leukodystrophy, neurological disorders. CNP encodes a major component of myelin and its CNS expression is exclusive to myelin-forming oligodendrocytes. Deficiency of CNP in mouse causes a lethal white matter neurodegenerative phenotype. However, a corresponding human phenotype has not been described to date. Here, we describe a multiplex consanguineous family from Oman in which multiple affected members display a remarkably consistent phenotype of neuroregression with profound brain white matter loss. A novel homozygous missense variant in CNP was identified by combined autozygome/exome analysis. Immunoblot analysis suggests that this is a null allele in patient fibroblasts, which display abnormal F-actin organization. Our results suggest the establishment of a novel CNP-related hypomyelinating leukodystrophy in humans.

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