2. Academic Validation
  3. A null mutation in TNIK defines a novel locus for intellectual disability

A null mutation in TNIK defines a novel locus for intellectual disability

  • Hum Genet. 2016 Jul;135(7):773-8. doi: 10.1007/s00439-016-1671-9.
Shams Anazi 1,  Hanan E Shamseldin 1,  Dhekra AlNaqeb 2,  Mohamed Abouelhoda 1 3,  Dorota Monies 1 3,  Mustafa A Salih 4,  Khalid Al-Rubeaan 5,  Fowzan S Alkuraya 6 7 8
Affiliations

Affiliations

  • 1 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 2 University Diabetes Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • 3 Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
  • 4 Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • 5 University Diabetes Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia. [email protected].
  • 6 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. [email protected].
  • 7 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. [email protected].
  • 8 Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. [email protected].
PMID: 27106596 DOI: 10.1007/s00439-016-1671-9
Abstract

Intellectual disability (ID) is one of the most common disabilities and, although many genes have been implicated in its etiology, the genetic heterogeneity of ID continues to expand. The purpose of the study was to describe a novel autosomal recessive non-syndromic ID locus. Autozygome and linkage analysis, and exome sequencing followed by RNA and protein analysis of the candidate disease gene were performed. We describe two multiplex consanguineous families with non-syndromic ID phenotype, which maps to a critical linkage locus on 3q26. Exome sequencing of the index in each family revealed the same homozygous truncating mutation in TNIK that results in complete loss of the protein. TNIK is a kinase with a well-established role in dendrite development and synaptic transmission. The phenotype we observe in human patients who lack TNIK is consistent with the previously published Tnik (-/-) phenotype in the murine model. Our data strongly implicate TNIK deficiency in the causation of ID in humans.

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