CNP deficiency causes severe hypomyelinating leukodystrophy in humans

Lama Al-Abdi, Fathiya Al Murshedi, Alaa Elmanzalawy, Asila Al Habsi, Rana Helaby, Anuradha Ganesh, Niema Ibrahim, Nisha Patel, Fowzan S. Alkuraya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)615-622
Number of pages8
JournalHuman Genetics
Issue number5
Publication statusPublished - May 1 2020

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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