Clinical, Radiological, and Genetic Characterization of a Patient with a Novel Homoallelic Loss-of-Function Variant in DNM1

Ruqaiah AlTassan, Hanan AlQudairy, Rakan Alromayan, Abdullah Alfalah, Omar A. AlHarbi, Ana C. González-Álvarez, Stefan T. Arold, Namik Kaya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Heterozygous pathogenic variants in DNM1 are linked to an autosomal dominant form of epileptic encephalopathy. Recently, homozygous loss-of-function variants in DNM1 were reported to cause an autosomal recessive form of developmental and epileptic encephalopathy in unrelated patients. Here, we investigated a singleton from a first-degree cousin marriage who presented with facial dysmorphism, global developmental delay, seizure disorder, and nystagmus. To identify the involvement of any likely genetic cause, diagnostic clinical exome sequencing was performed. Comprehensive filtering revealed a single plausible candidate variant in DNM1. Sanger sequencing of the trio, the patient, and her parents, confirmed the full segregation of the variant. The variant is a deletion leading to a premature stop codon and is predicted to cause a protein truncation. Structural modeling implicated a complete loss of function of the Dynamin 1 (DNM1). Such mutation is predicted to impair the nucleotide binding, dimer formation, and GTPase activity of DNM1. Our study expands the phenotypic spectrum of pathogenic homozygous loss-of-function variants in DNM1.

Original languageEnglish (US)
Article number2252
Issue number12
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This research was funded by the King Salman Center for Disability Research (KSCDR), Award No. KFSHRC-RAC: 2180004 (Namik Kaya), and the King Abdullah University of Science and Technology (KAUST), Award No. FCC/1/1976-25 and REI/1/4446-01 from the Office of Sponsored Research (OSR) (Stefan T. Arold).

Funding Information:
We are grateful to the participating patient and her family. We also extend our thanks to the Core Laboratories at the Centre for Genomic Medicine, Research Advisory Council Committees, and the KFSHRC Purchasing Departments for facilitating and expediting our requests. We especially thank the King Salman Center for Disability Research for the generous grant support to Namik Kaya.

Publisher Copyright:
© 2022 by the authors.


  • developmental delay
  • DNM1
  • epileptic encephalopathy
  • homozygous
  • intellectual disability
  • loss of function
  • novel deleterious variant
  • Sanger sequencing
  • whole-exome sequencing (WES)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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